Journal: bioRxiv

Article Title: A functional map of CDK-drug interactions at single amino acid resolution

doi: 10.1101/2025.11.02.685764

Figure Lengend Snippet: a) Scatterplot of median gRNA enrichment (log 2 fold-change) in the presence of BSJ-4-116 relative to DMSO-treated control. Each dot represents a gRNA, filtered to exclude gRNAs below 10% sensor editing and with a base mean count ≤ 100. Hits labelled with FDR < 0.1 & LFC ≥ 2. ABE screen results shown in purple; CBE in blue. Regions shaded blue indicate ATP binding site residues. b) Same as (a), but for HQ461-treated cells. c) Visualization of the top resistance variants in BSJ-4-116- and HQ461-treated cell pools. Maximum likelihood estimate of sensor editing rate shown as amino acid logo plot. d) Visualization of enriched residues in CDK12 in complex with HQ461 and DDB1. Colors indicate enrichment in 1 (salmon), 2 (red), or all drugs (purple), or HQ461 specifically (gold). PDB: 8BUG. e) Same as (d), but visualizing CDK13 hits. PDB: 7NXJ (with DDB1 superimposed from PDB: 8BUG). f) Dose-response curves of indicated variants when treated with BSJ-4-116 (top), CDK12-IN-2 (middle), and HQ461 (bottom). g) Visualization of top resistance variants in CDK2/4/6. Showing variants with FDR < .01 in at least one treatment condition. Maximum likelihood estimate of sensor editing rate shown as amino acid logo plot. h-j) Structural visualization of CDK4-cyclin D3 bound to abemaciclib (h), CDK6-cyclin D3 bound to abemaciclib (i), and CDK2-cyclin E complex bound to PF-06873600 (j), with resistance variants highlighted in purple. PDB: 7SJ3, 5L2S, 7KJS. Cyclin D3 in CDK6 structure (i) is superimposed from CDK4 structure (7SJ3). k) Endogenous allele frequency of CDK4, CDK2, and CDK6 variants before and after selection with 5 µM Abemaciclib, 10 µM Tagtociclib, or 10 µM Palbociclib. Sanger sequencing quantified with EditR software.

Article Snippet: KI-CDK9d-32 and KI-CDK9d-32N were provided by the Koehler lab. All other compounds were ordered from MedChemExpress (MCE) or SelleckChem (Selleck), with the following catalogue numbers: KB-0742 (MCE cat. no. HY-137478A), SY-5609 (MCE cat. no. HY-138293), Senexin B (MCE cat. no. HY-101800), SEL120 (Selleck cat. no. S8840), BSJ-4-116 (MCE cat. no. HY-139039), CDK12-IN-2, (MCE cat. no. HY-112626), HQ461 (MCE cat. no. HY-144981), Ribociclib (MCE cat. no. HY-15777), Palbociclib (MCE cat. no. HY-50767A), Abemaciclib (MCE cat. no. HY-16297), Atirmociclib (Selleck cat. no. E1495), Tagtociclib (MCE cat. no. HY-137894A), and INX-315 (MCE cat. no. HY-162001).

Techniques: Control, Binding Assay, Selection, Sequencing, Software

Journal: bioRxiv

Article Title: A functional map of CDK-drug interactions at single amino acid resolution

doi: 10.1101/2025.11.02.685764

Figure Lengend Snippet: Scatterplots of median gRNA enrichment (log 2 fold-change) in the presence of a) Ribociclib, b) Palbociclib, c) Abemaciclib, d) Atirmociclib, e) INX-315, or f) Tagtociclib relative to DMSO-treated control. Each dot represents a gRNA, filtered to exclude gRNAs below 10% sensor editing and with a base mean count ≤ 100. Hits labelled with FDR < 0.1 & LFC ≥ 1. ABE screen results shown in purple; CBE in blue. Regions shaded blue indicate ATP binding site residues.

Article Snippet: KI-CDK9d-32 and KI-CDK9d-32N were provided by the Koehler lab. All other compounds were ordered from MedChemExpress (MCE) or SelleckChem (Selleck), with the following catalogue numbers: KB-0742 (MCE cat. no. HY-137478A), SY-5609 (MCE cat. no. HY-138293), Senexin B (MCE cat. no. HY-101800), SEL120 (Selleck cat. no. S8840), BSJ-4-116 (MCE cat. no. HY-139039), CDK12-IN-2, (MCE cat. no. HY-112626), HQ461 (MCE cat. no. HY-144981), Ribociclib (MCE cat. no. HY-15777), Palbociclib (MCE cat. no. HY-50767A), Abemaciclib (MCE cat. no. HY-16297), Atirmociclib (Selleck cat. no. E1495), Tagtociclib (MCE cat. no. HY-137894A), and INX-315 (MCE cat. no. HY-162001).

Techniques: Control, Binding Assay

Journal: Pharmaceuticals

Article Title: Virtual Screening, Molecular Dynamics, and Mechanism Study of Homeodomain-Interacting Protein Kinase 2 Inhibitor in Renal Fibroblasts

doi: 10.3390/ph17111420

Figure Lengend Snippet: Inhibitory activities of compounds inhibiting renal cell proliferation or HIPK2.

Article Snippet: Abemaciclib Mesylate (LY2835219, CAS ID: 1231930-82-7) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China).

Techniques:

Journal: Pharmaceuticals

Article Title: Virtual Screening, Molecular Dynamics, and Mechanism Study of Homeodomain-Interacting Protein Kinase 2 Inhibitor in Renal Fibroblasts

doi: 10.3390/ph17111420

Figure Lengend Snippet: Interaction diagrams derived from 200 ns MD simulation trajectories, depicting plots of HIPK2 with Abemaciclib and CHR-6494. The blue regions represent Abemaciclib–HIPK2, while the red regions represent CHR-6494-HIPK2. ( A ) The plot of RMSD values over 200 ns for Abemaciclib–HIPK2 and CHR-6494-HIPK2. ( B ) The plot of RMSF values over 200 ns for Abemaciclib–HIPK2 and CHR-6494-HIPK2. ( C ) The plot of RMSF values over 200 ns for Abemaciclib and CHR-6494. ( D ) The plot of hydrogen bond numbers over 200 ns for Abemaciclib and CHR-6494 bound to HIPK2. ( E ) The plot of binding energy from 120 to 140 ns for Abemaciclib–HIPK2 and CHR-6494-HIPK2, calculated by MM-PBSA. ( F ) The plot of ΔE MM (the total potential energy of the system) from 120 to 140 ns for Abemaciclib–HIPK2 and CHR-6494-HIPK2. ( G ) The plot of ΔE polar (polar interaction) from 120 to 140 ns for Abemaciclib–HIPK2 and CHR-6494-HIPK2. ( H ) The plot of ΔE nonpolar (nonpolar interaction) values from 120 to 140 ns for Abemaciclib–HIPK2 and CHR-6494-HIPK2. ( I ) The plot of interaction energy from 120 to 140 ns for Abemaciclib–HIPK2 and CHR-6494-HIPK2.

Article Snippet: Abemaciclib Mesylate (LY2835219, CAS ID: 1231930-82-7) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China).

Techniques: Derivative Assay, Binding Assay

Journal: Pharmaceuticals

Article Title: Virtual Screening, Molecular Dynamics, and Mechanism Study of Homeodomain-Interacting Protein Kinase 2 Inhibitor in Renal Fibroblasts

doi: 10.3390/ph17111420

Figure Lengend Snippet: CHR-6494 and Abemaciclib suppress the proliferation and migration of TGF-β-induced NRK-49F cells. ( A ) Representative images of the colony formation assay. ( B ) Representative images of the cell scratch assay. ( C ) Quantitative data analysis of colony numbers for Abemaciclib and CHR-6494 in NRK-49F cells induced by 10 ng/mL of TGF-β. ( D ) Quantitative data analysis of cell migration distance for Abemaciclib and CHR-6494 in NRK-49F cells induced by 10 ng/mL of TGF-β. Data are presented as mean ± SEM, n = 3; “ns” stands for no significant difference, **** p < 0.0001, *** p < 0.001, ** p < 0.01, * p < 0.05 versus the Control + TGF-β group.

Article Snippet: Abemaciclib Mesylate (LY2835219, CAS ID: 1231930-82-7) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China).

Techniques: Migration, Colony Assay, Wound Healing Assay, Control

Journal: Pharmaceuticals

Article Title: Virtual Screening, Molecular Dynamics, and Mechanism Study of Homeodomain-Interacting Protein Kinase 2 Inhibitor in Renal Fibroblasts

doi: 10.3390/ph17111420

Figure Lengend Snippet: CHR-6494 and Abemaciclib mitigate NF-κB activation in HK-2 cells treated with 10 ng/mL TNF-α for 24 h in vitro. ( A ) The expression levels of p-p65, p65, and IL-6 proteins were measured by Western blot analysis. ( B ) Quantification of the ratios of p-p65, p65, and IL-6 normalized to β-actin. ( C ) Quantification of the ratios of p-p65 normalized to p65. Data are presented as mean ± SEM, n = 3; ## p < 0.01, # p < 0.05 versus the Control group, **** p < 0.0001, *** p < 0.001, ** p < 0.01, versus the Control + TGF-β group.

Article Snippet: Abemaciclib Mesylate (LY2835219, CAS ID: 1231930-82-7) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China).

Techniques: Activation Assay, In Vitro, Expressing, Western Blot, Control

Journal: Pharmaceuticals

Article Title: Virtual Screening, Molecular Dynamics, and Mechanism Study of Homeodomain-Interacting Protein Kinase 2 Inhibitor in Renal Fibroblasts

doi: 10.3390/ph17111420

Figure Lengend Snippet: CHR-6494 and Abemaciclib enhance TGF-β-induced apoptosis in NRK-49F cells treated with 10 ng/mL of TGF-β for 24 h in vivo. ( A , C ) Scattergram of Abemaciclib and CHR-6494 on the apoptosis and ( B , D ) quantitative data analysis of apoptotic NRK-49F. “0/+,4/+,8/+,12/+,18/+” means NRK-49F cells after TGF-β stimulation, treated with different concentrations of Abemaciclib or CHR-6494. ( E ) The expression levels of caspase 3 and cleaved caspase 3 proteins were measured by Western blot analysis. ( F ) Quantification of the ratios of cleaved caspase 3 normalized to caspase 3. Data are presented as mean ± SEM, n = 3; “ns” stands for no significant difference, *** p < 0.001, ** p < 0.01, * p < 0.05 versus the Control + TGF-β group.

Article Snippet: Abemaciclib Mesylate (LY2835219, CAS ID: 1231930-82-7) was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Shanghai, China).

Techniques: In Vivo, Expressing, Western Blot, Control

Journal: eLife

Article Title: Proliferative exhausted CD8 + T cells exacerbate long-lasting anti-tumor effects in human papillomavirus-positive head and neck squamous cell carcinoma

doi: 10.7554/eLife.82705

Figure Lengend Snippet: ( a ) Single-cell transcriptomic profiling of HNSCC tumor microenvironment (TME). Twenty cell clusters are identified, colored by cell types. ( b ) The proliferation status of P-Tex and epithelial cells in violin plot. ( c ) The kernel density estimate distribution of proliferation markers (CDK4 and MKI67) and epithelial cancer cell markers (KRT15 and CD24) in uniform manifold approximation and projection (UMAP) plots. ( d ) The overall survival rate of HPV + /HPV - HNSCC patients in The Cancer Genome Atlas (TCGA) cohort related to the expression levels of CDK4 gene, adjusted for age and gender. ( e ) The proportion of P-Texs, T-Tex, and TEFF clusters in HPV + and HPV - samples in TCGA cohort by using the deconvolution algorithm; statistics were assessed by Chi-square tests. Marker genes that were used to define cell clusters in ( a ) are deconvolved into the TCGA data to obtain the proportion of P-Texs, T-Tex, and Teff clusters in the TCGA cohort. ( f ) The cell viability of P-Tex and cancer epithelial cells assessed by CCK8 experiment after Abemaciclib treated in vitro. ***: p<0.001, **: p<0.01, *: p<0.05.

Article Snippet: Chemical compound, drug , Abemaciclib (LY2835219) , Topscience , Cat#T2381 , .

Techniques: Expressing, Marker, In Vitro

Journal: eLife

Article Title: Proliferative exhausted CD8 + T cells exacerbate long-lasting anti-tumor effects in human papillomavirus-positive head and neck squamous cell carcinoma

doi: 10.7554/eLife.82705

Figure Lengend Snippet:

Article Snippet: Chemical compound, drug , Abemaciclib (LY2835219) , Topscience , Cat#T2381 , .

Techniques: Sequencing, CCK-8 Assay, Software