Journal: Nature reviews. Clinical oncology

Article Title: Vessel calibre—a potential MRI biomarker of tumour response in clinical trials

doi: 10.1038/nrclinonc.2014.126

Figure Lengend Snippet: Preclinical antivascular and antiangiogenic studies that used vessel-calibre MRI

Article Snippet: Sunitinib (multitarget RTK inhibitor); 60 mg/kg per day , MDA-MB-435 melanoma in mice (10) 118 , ↓ ( P <0.05) , ↓ ( P <0.05) , Day 7.

Techniques: Inhibition, Disruption

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: The regulatory subunits of CDK5.

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques: Clinical Proteomics, Membrane, Binding Assay, Activity Assay

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: The mechanism of Cdk5 activation. The mechanism of Cdk5 activation. CDK5 alone is an inert catalyst subunit. CDK5 is activated by the p35 CDK5 activator and moves to the membrane as p35 binds to the membrane through myristoylation of the N-terminal region. p35 is a short-lived protein that is broken down by proteasomes. When cells are stressed or met with death signal, calpain is activated and cuts p35 into p25 C-terminal fragments. The deletion of p10 prolongs the half-life of p25. CDK5/p25 can be separate from the membrane and phosphorylate additional proteins. (modified from Kimura et al. ).

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques: Activation Assay, Membrane, Modification

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: The regulation of CDK5 by posttranslational modification.

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques: Modification, Phospho-proteomics, Activity Assay, Activation Assay, Migration

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: The modulation of transcription factors by CDK5.

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques: Phospho-proteomics

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: Schematic of kinase pathway phosphorylating EPRS Ser886 and Ser999. IFN-γ–activated CDK5 phosphorylate EPRS, leading to the formation of the GAIT complex. This inhibits inflammatory mRNA translation. Abbreviations- interferon-gamma (IFNγ), glutamyl-prolyl tRNA synthetase (EPRS), IFN-γ–activated inhibitor of translation (GAIT), tRNA multisynthetase complex (MSC). (modified from Arif et al. ).

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques: Modification

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: A summary of the various cyclin-dependent kinase 5 (CDK5)-mediated biological processes. CDK5 plays important roles not only in the central nervous system but also in different biological processes. Functions in the central nervous system include synaptic function, axon guidance, cell adhesion, and neurodegenerative diseases. Functions outside of the central nervous system include androgen production, cell cycle, cancer cell proliferation/apoptosis, and tumour metastasis. Abbreviations- microtubule-associated proteins 1B (MAP1B), focal adhesion kinase (FAK), doublecortin (DCX), p21 activated kinase 1 (Pak-1), Wiskott-Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE-1), Eph receptor A4 (EphA4), transforming growth factor-β1′ (TGF-β1), retinoblastoma (Rb), E2F transcription factor 1 (E2F1). (modified from Shupp et al. ).

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques: Modification

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: Impacts of CDK5 on the hallmarks of cancer: Uncontrolled proliferative signalling, Overcome growth suppressors, escaping antitumor immune system evasion, replicative immortality, tumour promoting inflammation, invasion and metastasis, inducing angiogenesis, genomic instability and mutation, resisting programmed cell death, metabolic reprogramming. Through the effect on the target protein, CDK5 is conducive to tumour development and metastasis. Abbreviations: phorbol-12-myristate-13-acetate-induced protein 1 (Noxa), Signal transducer and activator of transcription 3 (STAT3), androgen receptor (AR), retinoblastoma (Rb), bridging integrator 1 (BIN1), programmed cell death ligand 1 (PD-L1), focal adhesion kinase (FAK), targeting protein for Xklp2 (TPX2), hypoxia-inducible factor-1α (HIF-1α), ataxia-telangiectasia mutated (ATM). (Line 516–525). This figure is adapted and modified from Lenjisa et al., and Stecca et al. [ , ].

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques: Mutagenesis, Modification

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: Structures of CDK5 inhibitors: roscovitine, flavopiridol, dinaciclib, olomoucine, purvalanol A, indurubin-3′, 20-223, AT7519.

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques:

Journal: Cancers

Article Title: The Role of CDK5 in Tumours and Tumour Microenvironments

doi: 10.3390/cancers13010101

Figure Lengend Snippet: IC 50 values of CDK5 inhibitors.

Article Snippet: We classify the CDK5 inhibitors as early pan CDK inhibitors, multitarget CDK5 inhibitors, and selective CDK5 inhibitors according to report of Whittaker et al.’s ( ) [ ].

Techniques:

Journal: Scientific Reports

Article Title: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

doi: 10.1038/srep16924

Figure Lengend Snippet: High-throughput computational screening pipeline to identify dual inhibitors of EGFR kinase and BRD4(1).

Article Snippet: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.

Techniques: High Throughput Screening Assay

Journal: Scientific Reports

Article Title: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

doi: 10.1038/srep16924

Figure Lengend Snippet: Evaluation and characterization of the BRD4 docking data fusion model.

Article Snippet: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.

Techniques:

Journal: Scientific Reports

Article Title: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

doi: 10.1038/srep16924

Figure Lengend Snippet: Docking scores versus reported BRD4 pActivities (pIC 50 /pK d /pK i ) and Pearson correlation results of representative BRD4 inhibitors by chemotypes.

Article Snippet: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.

Techniques:

Journal: Scientific Reports

Article Title: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

doi: 10.1038/srep16924

Figure Lengend Snippet: Circles represent purchased compounds tested in the BRD4(1) assay, categorized by their activity against BRD4 and EGFR. Only compounds that were confirmed active against BRD4 were further tested for activity against EGFR; any of the black circles therefore could also be EGFR actives.

Article Snippet: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.

Techniques: Activity Assay

Journal: Scientific Reports

Article Title: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

doi: 10.1038/srep16924

Figure Lengend Snippet: ( A ) Average concentration-response profile of compound 2870 and known BRD4 inhibitor I-BET151 using the BRD4(1) biochemical alpha screen assay (n = 3). Emission data was normalized using DMSO and is reported as % response. Average IC 50 of 2870 was found to be 9.02 μ M against BRD4(1). ( B ) The EGFR kinase radioisotope filter binding assay was performed at a substrate concentration of 10 μ M against 2870 and Staurosporine (n = 3). Average IC 50 of 2870 was found to be 0.044 μ M against EGFR kinase.

Article Snippet: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.

Techniques: Concentration Assay, Filter-binding Assay

Journal: Scientific Reports

Article Title: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

doi: 10.1038/srep16924

Figure Lengend Snippet: Activity from the alphascreen assay against BRD4(1) and closest topological similarity to known BRD4(1) binders is also shown. Five other compounds comprising the same sulfonamide scaffold as 8302 were also confirmed actives but are not displayed.

Article Snippet: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.

Techniques: Activity Assay, Amplified Luminescent Proximity Homogenous Assay

Journal: Scientific Reports

Article Title: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

doi: 10.1038/srep16924

Figure Lengend Snippet: Binding affinity of 2870.

Article Snippet: Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4.

Techniques: Binding Assay