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. Author manuscript; available in PMC: 2024 Feb 16.
Published in final edited form as: Cell Chem Biol. 2023 Feb 6;30(2):203–213.e17. doi: 10.1016/j.chembiol.2023.01.004

Figure 2. Mechanism of action of 955 in degrading CDK9.

Figure 2.

(A) Pre-treatment with the proteasome inhibitor MG132 or bortezomib blocks CDK9 degradation by 955; (B) Pre-treatment with the lysosome inhibitor Baf-A1 or chloroquine does not block CDK9 degradation by 955; (C) Pre-treatment with pan-caspase inhibitor QVD does not block CDK9 degradation by 955; (D-E) Pre-treatment with E1 inhibitor TAK-243 (D) or PYR-41 (E) blocks CDK9 degradation by 955; (F) Pre-treatment with neddylation inhibitor MLN4924 blocks CDK9 degradation by 955. (G) The structure of 336 illustrates the reduction of the C2-C3 and C7-C8 double bonds of PL in comparison with 955; (H) 955, but not 336, can degrade CDK9. All the experiments were performed in MOLT4 cells. Representative immunoblots are shown and β-actin was used as a loading control in all immunoblot analyses. The quantification of the relative CDK9 protein content in the immunoblots is presented as mean ± SD (n = 2 biologically independent experiments) in the bar graph (bottom panel). Statistical significance was calculated with unpaired two-tailed Student’s t-tests. *P < 0.05; **P < 0.01; NS: not significant. See also Figure S3.