Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: PROTAC datasets and their characterization. (A) Overview of the structural composition of the PROTACs in the VHL ( n = 115) and CRBN ( n = 113) sets. (B) Distribution of the molecular descriptors of Lipinski’s and Veber’s guidelines for the two sets. Box plots show the 50 th percentiles as horizontal bars, the 25 th and 75 th percentiles as boxes, and the 25 th percentile minus 1.5 × the interquartile range and the 75 th percentile plus 1.5 × the interquartile range as whiskers. Outliers are shown both as red dots and as circles in the color of the appropriate descriptor. (C) Score plots of the first two principal components from principal component analyses (PCAs), which describe 71.5% of the variance for the VHL set and 74.9% of the variance for CRBN. The PCAs were based on the 17 descriptors calculated for each PROTAC, which were subsequently used for construction of the permeability models (cf. Figure A). Ellipses in green, yellow, and red shading show the 95% confidence intervals for highly, moderately, and lowly permeable compounds, respectively. The centroid of each permeability class is indicated with a large circle in the color of the respective class. The contributions of individual descriptors to the PCAs are indicated by arrows.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Permeability

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: (A) Principal component analysis comparing the chemical space of PROTACs in the public domain (red and cyan circles) to our in-house set (green circles). Public PROTACs that are within the applicability domain of the in-house set are in red, while those outside are in cyan. The centroids for each set are indicated with a large circle in the color of the respective set. (B) Examples of molecular structures of two PROTACs that reside outside the chemical space of the in-house set. The descriptors of the Lipinski and Veber guidelines are given below the structure of each PROTAC.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques:

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Cohen’s kappa statistics for internal test set validation of different BCMs for three permeability scenarios of (A) CRBN and (B) VHL PROTACs. Box plots show the kappa values from 25 random seedlings, while the yellow circles show the kappa values from 10-fold cross validation. In the box plots, the 50 th percentiles are marked as horizontal bars, the 25 th and 75 th percentiles as boxes, and the 25 th percentile minus 1.5 × the interquartile range and the 75 th percentile plus 1.5 × the interquartile range as whiskers. Outliers are shown both as black dots and as circles in the color of the method used to build the model. DT: decision tree, kNN: kappa nearest neighbor, RF: random forest, and SVM: support vector machine. Classification models can be assessed using the following cut-offs for Cohen’s kappa: κ < 0: no agreement, 0–0.19: poor agreement, 0.20–0.39: fair agreement, 0.40–0.59: moderate agreement, and 0.60–0.79 and 0.80–1.00: substantial to perfect agreement.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Biomarker Discovery, Permeability, Plasmid Preparation

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Probability distribution of true predictions for the random forest models built using the original VHL dataset. PROTACs having a probability smaller or larger than 0.5 were correctly classified as having low (orange) or high (green) permeability, respectively. A probability of 0.9–1.0 indicates that the compound was predicted to have a high permeability with >90% probability. Similarly, a probability of 0–0.1 indicates that the compound was predicted to have a low permeability with >90% probability.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Permeability

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Number of compounds in the training sets of PROTACs used to construct BCMs (original and retrained set) and the datasets used as blinded test sets for validation of the models (blinded test sets 1 and 2). For each dataset, the distribution of compounds between VHL and CRBN PROTACs, as well as by permeability class, is given.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Construct, Biomarker Discovery, Permeability

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Cohen’s kappa coefficient for prediction of the permeability of the VHL and CRBN PROTACs in the blinded test set 1. The kappa coefficient is given for the three permeability scenarios for models constructed using the DT, kNN, and RF methods based on the original dataset and its SMOTE versions. Kappa coefficients have been color-coded using red-orange-yellow-green for values ranging from −0.3 to 0.7.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Permeability, Construct

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Cohen’s kappa statistics for internal validation of different retrained BCMs for three permeability scenarios of (A) CRBN and (B) VHL PROTACs in the retrained set. Box plots show the kappa values from 25 random seedlings, while the yellow circles show the kappa values from 10-fold cross validation. In the box plots, the 50 th percentiles are marked as horizontal bars, the 25 th and 75 th percentiles as boxes, and the 25 th percentile minus 1.5 × the interquartile range and the 75 th percentile plus 1.5 × the interquartile range as whiskers. Outliers are shown both as black dots and as circles in the color of the method used to build the model. DT: decision tree, kNN: kappa nearest neighbor, and RF: random forest. Classification models can be assessed using the following cut-offs for Cohen’s kappa: k < 0: no agreement, 0–0.19: poor agreement, 0.20–0.39: fair agreement, 0.40–0.59: moderate agreement, and 0.60–0.79 and 0.80–1.00: substantial to perfect agreement.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Biomarker Discovery, Permeability

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Cohen’s kappa coefficient for prediction of the permeability of the VHL PROTACs in the blinded test set 2 using models constructed with the (A) original training set and the (B) retraining set. The kappa coefficient is given for the three permeability scenarios for models constructed using the DT, kNN, and RF methods. Kappa coefficients have been color-coded using red-orange-yellow-green for values ranging from −0.30 to 0.70.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Permeability, Construct

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Contribution of the descriptors to the retrained RF models for prediction of the permeability of VHL PROTACs. The figure shows the mean values of the weight of each descriptor for permeability scenarios 1–3, with error bars indicating ± standard deviation. The weight of the contribution of each descriptor to the model was obtained from the 10-fold cross validation. The descriptors that contribute most to the model are indicated by the blue shading at a weight of ≥0.4. Color code: violet: countable descriptors, pink: chemical functionalities descriptors, and green: size and shape descriptors. Descriptor contributions for the individual models for scenarios 1–3 can be found in the Supporting Information, Figure S10B .

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Permeability, Standard Deviation, Biomarker Discovery

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Distribution of the molecular descriptors of Lipinski’s and Veber’s guidelines for the linker part ( n = 129) of the VHL PROTACs in the combined training set and blinded test set 1 ( n = 253). Distributions have been calculated for the linkers of the PROTACS in each of the three permeability classes. Box plots show the 50 th percentiles as horizontal bars, the 25 th and 75 th percentiles as boxes, and the 25 th percentile minus 1.5 × the interquartile range and the 75 th percentile plus 1.5 × the interquartile range as whiskers. Outliers are shown both as black dots. Statistical analysis was performed using Wilcoxon’s non-parametric test.

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Permeability

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Number of PROTACs Used for Data Analysis, Model Building, and Validation

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques:

Journal: ACS Omega

Article Title: Predictive Modeling of PROTAC Cell Permeability with Machine Learning

doi: 10.1021/acsomega.2c07717

Figure Lengend Snippet: Overview of Purities of the PROTACs Included in the Training and Tests Sets

Article Snippet: All PROTACs were prepared at Bayer AG, and their structures were confirmed by high-resolution mass spectrometry and 1 H NMR spectroscopy.

Techniques: Standard Deviation

Journal: bioRxiv

Article Title: PROTAC-mediated Degradation of HIV-1 Nef Efficiently Restores Cell-surface CD4 and MHC-I Expression and Blocks HIV-1 Replication

doi: 10.1101/2023.08.14.553289

Figure Lengend Snippet: The Cereblon (CRBN) ubiquitin E3 ligase complex ( left ) is a large multiprotein structure composed of RING-box protein 1 (RBX1), Cullin4 (CUL4), DNA damage binding protein 1 (DDB1), CRBN and an E2 subunit conjugated to ubiquitin (Ub). Heterobifunctional Nef PROTACs promote formation of a ternary complex between the HIV-1 Nef protein using existing hydroxypyrazole Nef-binding compounds ( red ) and the CRBN E3 complex via a CRBN ligand (exemplified by thalidomide, green). Ternary complex formation induces polyubiquitination of Nef and subsequent proteasomal degradation. The Nef PROTAC shown is analog FC-13182 ; favored positions for linker attachment on the Nef-binding moiety are indicated by the short black arrows .

Article Snippet: These results provide evidence that active Nef PROTACs induce ternary complexes of Nef with CRBN and are consistent with the results from the Nano-BRET and CEM-T4 assays.

Techniques: Ubiquitin Proteomics, Binding Assay

Journal: bioRxiv

Article Title: PROTAC-mediated Degradation of HIV-1 Nef Efficiently Restores Cell-surface CD4 and MHC-I Expression and Blocks HIV-1 Replication

doi: 10.1101/2023.08.14.553289

Figure Lengend Snippet: A) Assay principle. Nef is fused to nano-Luciferase (Nef-nLuc) and co-expressed with a ubiquitin-Halo tag fusion protein (Ub-Halo) in 293T cells. PROTACs promote ligation of Ub-Halo to Nef-nLuc, which is detected by bioluminescence resonance energy transfer (BRET) to the Halo Tag. B) Assessment of candidate Nef PROTACs in the NanoBRET assay. Each compound was assayed in quadruplicate and the average 618 nm to 460 nm fluorescence ratios (BRET signal for Ub incorporation normalized to Nef-nLuc levels) were normalized to the DMSO control and are presented as z-scores ± SD (error bars smaller than data points). PROTACs with z-scores ≥ 1.5 (numbered red points) along with analog FC-13887 were advanced to orthogonal assays for Nef degradation and inhibition of Nef function. z-score = (x - µ)/σ, where x = each individual value, µ = mean value, and σ = the standard deviation.

Article Snippet: These results provide evidence that active Nef PROTACs induce ternary complexes of Nef with CRBN and are consistent with the results from the Nano-BRET and CEM-T4 assays.

Techniques: Luciferase, Ubiquitin Proteomics, Ligation, Bioluminescence Resonance Energy Transfer, Fluorescence, Control, Inhibition, Standard Deviation

Journal: bioRxiv

Article Title: PROTAC-mediated Degradation of HIV-1 Nef Efficiently Restores Cell-surface CD4 and MHC-I Expression and Blocks HIV-1 Replication

doi: 10.1101/2023.08.14.553289

Figure Lengend Snippet: The human T cell line CEM-T4 was engineered to express a Nef-eGFP fusion protein under the control of a doxycycline (Dox) inducible promoter. In the absence of Dox, these cells express endogenous CD4 and MHC-I on their surface; addition of Dox induces Nef-eGFP expression which leads to receptor downregulation. A) Representative flow cytometry result with Nef PROTAC FC-14369 and cell surface CD4 staining. B) Active Nef PROTACs from the NanoBRET ubiquitination assay were screened for cell surface receptor rescue in triplicate. Bar height indicates the mean value ± SE; individual data points are also shown. The structures of the analogs with little to no activity in this assay ( FC-13890, FC-14373, FC-14379, FC-14388 ) are shown in the Supplemental Information, Figure S1.

Article Snippet: These results provide evidence that active Nef PROTACs induce ternary complexes of Nef with CRBN and are consistent with the results from the Nano-BRET and CEM-T4 assays.

Techniques: Control, Expressing, Flow Cytometry, Staining, Ubiquitin Proteomics, Cell Surface Receptor Assay, Activity Assay

Journal: bioRxiv

Article Title: PROTAC-mediated Degradation of HIV-1 Nef Efficiently Restores Cell-surface CD4 and MHC-I Expression and Blocks HIV-1 Replication

doi: 10.1101/2023.08.14.553289

Figure Lengend Snippet: A) Flow cytometry of Nef-eGFP protein loss. CEM/Nef-eGFP cells were treated with doxycycline to induce expression of Nef-eGFP under conditions that result in a moderate level of positive cells by flow cytometry (see Figure 3A). Triplicate cultures of cells were treated with the Nef PROTAC analogs indicated at a final concentration of 3 µM, and 24 h later the percent of cells showing loss of Nef-eGFP protein expression were calculated relative to the DMSO controls and are presented as the mean value ± SE; individual data points are also shown. B) Correlation analysis of cell-surface CD4 rescue vs. Nef-eGFP protein loss (red data points, left) and MHC-I rescue vs. Nef-eGFP protein loss (blue data points, right). CD4 rescue was best-fit by linear regression, while MHC-I rescue showed a plateau effect. C) Immunoblot analysis. Cells expressing Nef-eGFP were treated as in part A with the eight active PROTACs, and lysates were prepared 48 h later for immunoblot analysis with Nef and Actin antibodies. A representative blot is shown. D) Immunoblot analysis was performed in duplicate, and band intensities were quantified by LI-COR infrared imaging and used to calculate Nef to Actin protein expression ratios. The bar graph shows the mean value for each ratio along with the individual values. The structures of the analogs with little to no activity in this assay ( FC-13890, FC-14373, FC-14379, FC-14388 ) are shown in the Supplemental Information, Figure S1.

Article Snippet: These results provide evidence that active Nef PROTACs induce ternary complexes of Nef with CRBN and are consistent with the results from the Nano-BRET and CEM-T4 assays.

Techniques: Flow Cytometry, Expressing, Concentration Assay, Western Blot, Imaging, Activity Assay

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: Chemical structures of representative NSD2 inhibitors and degraders 10–16.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: The biological functions of NSD2 and underlying mechanisms.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: Overview of various cancers associated with NSD lysine methyltransferases (KMTases) dysregulation.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques: Migration, Mutagenesis, Activity Assay, Transformation Assay, Expressing, DNA Synthesis

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: Crystal structure of compound 50 (MR837) in complex with NSD2-PWWP1 domain (PDB ID: 6UE6). Hydrogen bonds formed between 50 and the key residues in the NSD2-PWWP1 domain are highlighted by red dashed lines. Compound 50 is shown as yellow sticks. Key residues ALA-270, TYR-233, TRP-236, PHE-266, and VAL-230 in the NSD2-PWWP1 domain are shown as green sticks.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: (a) SAM crystal structure in complex with NSD2-SET domain (PDB ID: 5LSU). SAM is shown as cyan sticks; (b) Crystal structure of DNA in complex with NSD2-PWWP1 domain (PDB ID: 5VC8). The key residues LYS-304, LYS-309, and LYS-312 in NSD2-PWWP1 domain that form direct electrostatic interactions with the DNA phosphate backbone are shown as cyan sticks; and (c) The structures of three NSD2 isoforms (NSD2-long, NSD2-short, and RE-IIBP) that are composed of multiple domains, including PWWP domain, PHD domain, SET domain (AWS/pre-SET, SET, and post-SET), etc.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: (a) Crystal structure of compound 51 (MRT866) in complex with NSD2-PWWP1 domain (PDB ID: 7MDN). Red dash lines highlight the hydrogen bonds between compound 51 and the key residues in NSD2-PWWP1 domain. Compound 51 is shown as yellow sticks. Key residues ALA-270, GLN-321, TYR-233, TRP-236, and PHE-266 in the NSD2-PWWP1 domain are shown as green sticks. (b) Crystal structure of compound 14 (UNC6934) in complex with NSD2-PWWP1 domain (PDB ID: 6XCG). Red dash lines highlight the hydrogen bonds formed between compound 14 and the key residues in NSD2-PWWP1 domain. Compound 14 is shown as yellow sticks. Key residues ALA-270, GLN-321, TYR-233, ARG-273, TRP-236, and PHE-266 in the NSD2-PWWP1 domain are shown as green sticks.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: Crystal structure of compound 54 in complex with NSD2-PWWP1 domain (PDB ID: 7VLN). Hydrogen bonds formed between compound 54 and the key residues in the NSD2-PWWP1 domain are highlighted by red dashed lines. Compound 54 is shown as yellow sticks. Key residues ALA-270, ASP-269, TYR-233, GLU-291, and GLU-272 in the NSD2-PWWP1 domain are shown as green sticks.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques:

Journal: Journal of medicinal chemistry

Article Title: Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

doi: 10.1021/acs.jmedchem.3c00948

Figure Lengend Snippet: Crystal structure of compound 14 (UNC6934) in complex with NSD2-PWWP1 domain (PDB ID: 6XCG). Compound 14 is shown as green sticks, and the red dashed circle highlights the pyrimidine ring that points into the solvent-exposed region.

Article Snippet: Both NSD2 and its target gene HDAC2 were revealed to activate the NF-κB signaling pathway inducing the occurrence and progression of inflammation by promoting the release of proinflammatory cytokines.204 Meanwhile, NSD2 can modulate the envelope protein (protein E) of SARS-CoV2 via interactions with BRD4, suggesting that NSD2 may play an important role in the progression of SARS-CoV2.204 Proteolysis protein chimeras (PROTACs) targeting NSD2 degradation are being developed as valuable tools to explore the role of NSD2 in SARS-CoV2 and/or as potential therapeutic agents to treat COVID-19, a SARS-CoV2-related coronavirus disease (https://www.mitacs.ca/en/projects/development-targeted-degradation-nuclear-receptor-binding-set-domain-protein-2-nsd2).

Techniques: Solvent

Journal: Current research in chemical biology

Article Title: Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development

doi: 10.1016/j.crchbi.2022.100029

Figure Lengend Snippet: Poseltinib-based reversible covalent BTK PROTACs cannot induce BTK degradation in cells. a-e . Mino cells were treated with indicated compounds at 0, 1.6, 8, 40, 200, and 1000 nM for 24 h, followed by Western blotting for BTK. PS-RC-1, PS-RC-2, PS-RC-3, and PS-RC-4 are poseltinib-based reversible covalent BTK PROTACs. DD-03-171 is a BTK degrader developed by the Gray group and used as a positive control. f . HEK-293T cells stably expressing a BTK-nLuc fusion protein were treated with indicated compounds (same as in a-e ) for 24 h. The BTK degradation was determined by evaluating luminescence signals of NanoLuc. The DC 50 (concentration of PROTACs required to achieve 50% degradation of the target protein) and D max (maximum level of target protein can be degraded by PROTACs) values obtained through this assay are listed in .

Article Snippet: Pike et al. analyzed the oral bioavailability of PROTACs across a diverse set of projects at AstraZeneca and found that high oral bioavailability (>30%) can be achieved among approximately one third of CRBN-targeted PROTACs, while VHL-targeted PROTACs have no more than 3% of oral bioavailability ( ).

Techniques: Western Blot, Positive Control, Stable Transfection, Expressing, Concentration Assay

Journal: Current research in chemical biology

Article Title: Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development

doi: 10.1016/j.crchbi.2022.100029

Figure Lengend Snippet: Degradation of BTK induced by reversible covalent BTK PROTACs.

Article Snippet: Pike et al. analyzed the oral bioavailability of PROTACs across a diverse set of projects at AstraZeneca and found that high oral bioavailability (>30%) can be achieved among approximately one third of CRBN-targeted PROTACs, while VHL-targeted PROTACs have no more than 3% of oral bioavailability ( ).

Techniques: Binding Assay

Journal: Current research in chemical biology

Article Title: Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development

doi: 10.1016/j.crchbi.2022.100029

Figure Lengend Snippet: Toxicities of poseltinib-based BTK PROTACs in cells and their binding affinities to BTK. a-b . MOLM14 and Mino cells were treated with serially diluted poseltinib and PS-RC-1 to PS-RC-4 for 72 h, followed by Alarma Blue assay to quantify the cell viabilities. c . Three MCL cell lines, including Mino, Jeko-1, and Rec-R cells, were treated with serially diluted PS-RC-1 for 72 h, followed by Alarma Blue assay to quantify the cell viabilities. d . TR-FRET based binding kinetics assay between poseltinib and BTK. Serial dilutions of poseltinib mixed with 2 nM of His-BTK, 0.3 nM Tb-anti-His, and 150 nM of BTK-BODIPY tracer. e. BTK binding affinity assays for poseltinib-based PROTACs (PS-RC-1 to PS-RC-4), following the same protocol as described in d . After 2 h incubation, TR-FRET signals were measured. The IC 50 values were listed in f . PS-RC-1 serves as a molecular glue to inhibit growth in Mino cells. Mino cells were pre-treated with a large excess of PS-RC-Ctrl (2 μM or 10 μM), followed by PS-RC-1 incubation for 72 h. The cell viabilities were quantified using an Alarma Blue assay. For cell viability assays, data represent mean ± SD (n = 3) and the IC 50 values are defined as compound concentrations that reduce cell viabilities by 50%. For BTK binding assays, data represent mean ± SD (n = 3) and the IC 50 values are defined as compound concentrations that reduce tracer binding by 50%. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Pike et al. analyzed the oral bioavailability of PROTACs across a diverse set of projects at AstraZeneca and found that high oral bioavailability (>30%) can be achieved among approximately one third of CRBN-targeted PROTACs, while VHL-targeted PROTACs have no more than 3% of oral bioavailability ( ).

Techniques: Binding Assay, Incubation

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The researches on PROTAC from 2001 to 2021. a The publications on PROTACs from 2001 to 2021. b The structure of ARV-110 and ARV-471 . c The comparison of PROTAC targets on different diseases between 2001–2019 and 2001–2021. d Classification and percentage of degradable kinases

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques: Comparison

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting AR

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting BRAF and BRAF V600E

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting EGFR

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The summary and comparison of PROTACs targeting EGFR

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques: Comparison

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting eIF4E

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting ER

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting BRD

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting IGF-1R and Src

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting KRAS G12C

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting MEK

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting p38

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting PDEδ

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting SHP2

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting PARP1

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting AKT

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting ALK

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting Bcl-xl

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The summary and comparison of PROTACs targeting Bcl-xl

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques: Comparison

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting BCR-ABL

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The summary and comparison of PROTACs targeting BCR-ABL

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques: Comparison

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting FAK

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting MDM2

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting FLT3

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting JAK

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The summary and comparison of PROTACs targeting BRD

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques: Comparison

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting HDAC

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting PRC2 (EZH2, EED)

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting WDR5

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting Aurora A

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting CDK2

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting CDK2/4/6

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting CDK9

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting CDK12

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting CRBN

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting BTK

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The summary and comparison of PROTACs targeting BTK

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques: Comparison

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting PD-L1

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting SMARCA2/4

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting pan-coronavirus antiviral

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting SARS-CoV-2

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting HDAC3

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting H-PGDS

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting IRAK4

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting neurodegenerative diseases

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs targeting Cas protein, HMGCR and VEGFR2

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs of antibody-PROTAC

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs of aptamer-PROTAC conjugates

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTAC of dual-target PROTACs

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs of Folate-Caged PROTACs

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques:

Journal: Signal Transduction and Targeted Therapy

Article Title: PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

doi: 10.1038/s41392-022-00999-9

Figure Lengend Snippet: The representative PROTACs of TF-PROTACS

Article Snippet: Fig. 82 The representative PROTACs of antibody-PROTAC Researchers from Genentech have also developed a series of Ab-PROTAC conjugates based on different antibodies and BRD4 degraders.

Techniques: