SHR5428 is an orally active, selective, noncovalent inhibitor of CDK7, displaying potent enzymatic inhibition (IC50 = 2.3 nM) and effectively suppressing cellular activity in triple-negative breast cancer MDA-MB-468 cells (IC50 = 6.6 nM) [1].

CDK12:1.11 μM, CDK1:>100 μM, CDK7:0.005 μM, CDK4:3.87 μM, CDK9:8.30 μM, CDK2:8.99 μM, CDK6:5.89 μM

SHR5428 administered orally at doses of 3-30 mg/kg once daily for 21 days demonstrated dose-dependent tumor growth inhibition [1]. A single oral dose of SHR5428 at 2 mg/kg exhibited favorable pharmacokinetic profiles across various species, including mice, rats, and dogs [1]. The pharmacokinetic parameters of SHR5428 in these species were as follows: Maximum concentration (Cmax) in ng/mL was 116 for mice, 120 for rats, and 543 for dogs; the area under the curve (AUC) in ng/mL*h was 139 for mice, 556 for rats, and 4101 for dogs; the half-life (t1/2) in hours was 0.7 for mice, 2.6 for rats, and 4.9 for dogs; and bioavailability (F%) was 32% for mice, 44% for rats, and 92% for dogs [1].