BSJ-01-175 is a potent and selective CDK12/13 covalent inhibitor. BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells [1].
In Vivo, BSJ-01–175 (10 mg/kg; i.p.; daily for 3 weeks) leads to a significant suppression of tumor growth throughout 3 weeks of drug treatment period[1]. Assessment of Pharmacokinetics (PK) profile of BSJ-01-175 in mouse[1]. Route Dose (mg/kg) Tmax (h) Cmax (ng/mL) AUClast (h•ng/mL) T1/2 (h) CL (mL/min/kg) VSS (L/kg) F (%) IV 3 1511 1832 2.2 24.9 3.9 PO 10 2 272 1043 17
In Vitro, BSJ-01–175 (0-10 μM; 72 hours) causes a 5-fold increase in cell viability compared to the wild type (WT), indicating strong dependence on covalent bond formation with Cys1039[1]. BSJ-01–175 (0-10 μM; 72 hours) slightly decreases the activity of TC71 Ewing sarcoma cells compared to THZ531[1]. BSJ-01–175 (0-5 μM) specifically targets CDK12/13 and suppresses the transcription of BRAC1 and BRAC2[1].
References:
[1]. Jiang B, et al. Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma. Eur J Med Chem. 2021;221:113481.
In Vivo, BSJ-01–175 (10 mg/kg; i.p.; daily for 3 weeks) leads to a significant suppression of tumor growth throughout 3 weeks of drug treatment period[1]. Assessment of Pharmacokinetics (PK) profile of BSJ-01-175 in mouse[1]. Route Dose (mg/kg) Tmax (h) Cmax (ng/mL) AUClast (h•ng/mL) T1/2 (h) CL (mL/min/kg) VSS (L/kg) F (%) IV 3 1511 1832 2.2 24.9 3.9 PO 10 2 272 1043 17
In Vitro, BSJ-01–175 (0-10 μM; 72 hours) causes a 5-fold increase in cell viability compared to the wild type (WT), indicating strong dependence on covalent bond formation with Cys1039[1]. BSJ-01–175 (0-10 μM; 72 hours) slightly decreases the activity of TC71 Ewing sarcoma cells compared to THZ531[1]. BSJ-01–175 (0-5 μM) specifically targets CDK12/13 and suppresses the transcription of BRAC1 and BRAC2[1].
References:
[1]. Jiang B, et al. Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma. Eur J Med Chem. 2021;221:113481.