SY-5609 (CDK7-IN-3) is an orally active, highly selective, noncovalent CDK7 inhibitor with a KD of 0.065 nM. SY-5609 shows poor inhibition on CDK2 (Ki=2600 nM), CDK9 (Ki=960 nM), CDK12 (Ki=870 nM). SY-5609 induces apoptosis in tumor cells and has antitumor activity[2].In Vitro: SY-5609 (0.01-10000 nM; 72 hours) demonstrates strong antiproliferative effects in triple negative breast cancer (TNBC) and ovarian (OVA) cancer cells.
SY-5609 (100-500 nM; 48, 72 hours) induces apoptosis.
SY-5609 (100-500 nM; 48 hours) induces G2/M cell cycle arrest in HCC70 cells.
SY-5609 (25-500 nM; 6-48 hours) results in inhibition of the phosphorylation of CDK2 at Thr160 via loss of CAK function for 24 and 48 h.
SY-5609 (compound 101; 126.4 pM-4 μM; 72 hours) has an EC50 of 5.6 nM in HCC70 cell line[2].In Vivo: SY-5609 (2 mg/kg/day; orally; for 21 days) induces tumor regression over the 21-day dosing period.
Daily oral dosing of 2 mg/kg SY-5609 in mice provided a plasma exposure of 261.28 ng h/mL with a Cmax of 50.67 ng/mL (103 nM) and an elimination half-life of 3.33 h.