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. 2020 Nov 1;34(21-22):1452–1473. doi: 10.1101/gad.341545.120

Figure 1.

Figure 1.

SY-351 is a potent and highly selective covalent inhibitor of human CDK7. (A) SY-351 structure. (B) Kinome selectivity in A549 cell lysate, with 0.2 µM and 1 µM SY-351. The top six hits shown are kinases inhibited > 50% by 1 µM SY-351. Note that SY-351 was used at 0.05 µM (50 nM) throughout this study. (C) CDK7 and CDK12 target occupancy in HL-60 cells after 1-h treatment. The SY-351 EC50 is 8.3 nM for CDK7 and 36 nM for CDK12. The SY-351 EC90 is 39 nM for CDK7 and 172 nM for CDK12. The dashed line indicates 50 nM SY-351, the dose used throughout this study. (D) SY-351 inhibition of active kinases CDK7/CCNH/MAT1, CDK2/CCNE1, CDK9/CCNT1, CDK12/CCNK at Km ATP for each enzyme. The best fit IC50 values are 23 nM, 321 nM, 226 nM, and 367 nM, respectively.