SR-5037 is an orally active CDK12 ( IC50 = 31 nM)/ CDK13 inhibitor and CycK ( DC50 = 30 nM; D max > 98%) molecular glue degrader. SR-5037 inhibits the enzymatic activity of CDK12 /CycK and CDK13 /CycK complexes. SR-5037 promotes the recruitment of DDB1 to the CDK12 /CycK complex, thereby triggering proteasome-mediated CycK degradation. SR-5037 degrades active CycK in mouse models of triple-negative breast cancer. SR-5037 can be used in the research of cancers such as triple-negative breast cancer [1].
In Vivo, SR-5037 (2-18 mg/kg; p.o.; single dose) induces dose-dependent depletion of cyclin K in orthotopic triple-negative breast cancer tumors in female NSG mice, with target modulation correlating with plasma drug concentration[1].
In Vitro, SR-5037 (1 μM) degrades CycK (DC50 = 30 nM; Dmax > 98%) and inhibits the kinase activities of WEE1 (59.8%), mTOR (50.6%) and CDK15 (49.2%)[1]. SR-5037 (0.000001-10 μM; 2 h (room temperature)) inhibits the enzymatic activity of purified human CDK12/CycK (IC50 = 58.7 nM, Kd = 139 nM) and CDK13/CycK (IC50 = 134.6 nM) complexes, and promotes the formation of a stable ternary complex between CDK12/CycK and DDB1 (Kd = 2.81 nM)[1]. SR-5037 (100 nM, 1-4 h) potently and rapidly induces the degradation of CycK in MDA-MB-231 cells[1]. SR-5037 (2 h) degrades cyclin K in HiBiT-CycK knock-in A549 cells, with a DC50 of 30 nM and a Dmax > 95%[1].
References:
[1]. Pandurangan T, et al. Structure-Activity and Structure-Degradation Relationship Studies of 2-Amino-6-(benzimidazol-2-ylmethyl)-N9-heteroarylpurines as Potent and Selective CDK12/13 Inhibitors and Cyclin K Degraders. J Med Chem. 2026 Feb 12;69(3):2287-2309.
In Vivo, SR-5037 (2-18 mg/kg; p.o.; single dose) induces dose-dependent depletion of cyclin K in orthotopic triple-negative breast cancer tumors in female NSG mice, with target modulation correlating with plasma drug concentration[1].
In Vitro, SR-5037 (1 μM) degrades CycK (DC50 = 30 nM; Dmax > 98%) and inhibits the kinase activities of WEE1 (59.8%), mTOR (50.6%) and CDK15 (49.2%)[1]. SR-5037 (0.000001-10 μM; 2 h (room temperature)) inhibits the enzymatic activity of purified human CDK12/CycK (IC50 = 58.7 nM, Kd = 139 nM) and CDK13/CycK (IC50 = 134.6 nM) complexes, and promotes the formation of a stable ternary complex between CDK12/CycK and DDB1 (Kd = 2.81 nM)[1]. SR-5037 (100 nM, 1-4 h) potently and rapidly induces the degradation of CycK in MDA-MB-231 cells[1]. SR-5037 (2 h) degrades cyclin K in HiBiT-CycK knock-in A549 cells, with a DC50 of 30 nM and a Dmax > 95%[1].
References:
[1]. Pandurangan T, et al. Structure-Activity and Structure-Degradation Relationship Studies of 2-Amino-6-(benzimidazol-2-ylmethyl)-N9-heteroarylpurines as Potent and Selective CDK12/13 Inhibitors and Cyclin K Degraders. J Med Chem. 2026 Feb 12;69(3):2287-2309.