recombinant proteins sr 4835 medchemexpress  (MedChemExpress)

Journal: EMBO Reports

Article Title: DDB1 engagement defines the selectivity of S656 analogs for cyclin K degradation over CDK inhibition

doi: 10.1038/s44319-025-00448-y

Figure Lengend Snippet: ( A ) Inhibitory profile of S656, CR8, SR4835, HQ461, NCT02, THZ531 and SNS-032 compounds across 40 primary AML specimens in dose response assays. IC 50 values were determined after 6 days of incubation and normalized to DMSO control. ( B ) Dot plot summarizing the IC 50 values and medians (red) obtained in the panel of 40 primary AMLs. ( C ) Heatmap representation and hierarchical clustering of IC 50 values from ( A ). Correlation between S656 and the other molecules is indicated. Relative color scheme uses the minimum and maximum IC 50 values in each row. .

Article Snippet: SR4835 , MedChemExpress , HY-130250.

Techniques: Incubation, Control

Journal: EMBO Reports

Article Title: DDB1 engagement defines the selectivity of S656 analogs for cyclin K degradation over CDK inhibition

doi: 10.1038/s44319-025-00448-y

Figure Lengend Snippet: ( A ) Dose response experiment to determine IC 50 values of the indicated compounds in OCI-AML5 cells expressing shRNAs targeting CDK1 , 2 , 4 , 7 , 9 , cyclin K or a control region (4 days incubation, mean +/− SD, n = 3, biological replicates, t test, P value = 0.0011 (sh ctrl vs sh Cyclin K) in CR8, P value = 0.0029 (sh ctrl vs sh Cyclin K) in SR4835, P value = 0.0011 (sh ctrl vs sh Cyclin K) in HQ461, P value = 0.0025 (sh ctrl vs sh CDK9) in SNS-032, P value = 0.0038 (sh ctrl vs sh CDK1) in S656, P value = 0.0253 (sh ctrl vs sh CDK9) in S656 and P value = 0.0004 (sh ctrl vs sh Cyclin K) in S656). ( B ) Dot plot representation of the IC 50 values of all S656 analogs (black) and control molecules (colors) in OCI-AML5 cells along with their efficiency to degrade cyclin K eGFP (percentage of degradation after 3 h incubation with 10 μM of compounds, compared to DMSO). Highest tested dose is 10000 nM. ( C ) Dot plot representation of the ratio of IC 50 values in OCI-AML5 expressing shRNA control or targeting CUL4A , and the percentage of cyclin K eGFP degradation (3 h incubation with 10 μM of compounds, compared to DMSO) for all active (IC 50 < 10000 nM) S656 analogs (black) and control molecules (colors). ( D ) Working model in which molecules with high affinity for DDB1 behave as cyclin K degraders while modifications of the left-hand side of the molecule, lowering or abolishing the interaction with DDB1, induce cytotoxicity through CDK inhibition. See also Appendix Fig. S . .

Article Snippet: SR4835 , MedChemExpress , HY-130250.

Techniques: Expressing, Control, Incubation, shRNA, Inhibition