[Description]:
Voruciclib hydrochloride is a clinical stage oral CDK9 inhibitor. Voruciclib hydrochloride represses expression of MCL-1 in multiple models of diffuse large B-cell lymphoma (DLBCL)[1].
[Related Catalog]:
[Target]
CDK9/CycT1:1.68 nM (Ki)
CDK9/cyc T2:0.626 nM (Ki)
CDK4/Cyc D1:3.96 nM (Ki)
CDK1/cycB:5.4 nM (Ki)
CDK1/cyc A:9.1 nM (Ki)
CDK6/cycD1:2.92 nM (Ki)
[In Vitro]
Voruciclib hydrochloride (0.5-5 µM; 6 hours) shows targeted downregulation of MCL-1 in both ABC and GCB subtypes[1]. Ki values for each target such as CDK9/cyc T2, CDK9/cyc T1, CDK6/cyc D1, CDK4/cyc D1, CDK1/cyc B, and CDK1/cyc A for Voruciclib hydrochloride are 0.626 nM, 1.68 nM, 2.92 nM, 3.96 nM, 5.4 nM, 9.1 nM, respectively[1]. Western Blot Analysis Cell Line: U2932, RIVA, OCI-LY10 cells (ABC subtype), NU-DHL-1, SU-DHL-4, SU-DHL-6 cells (GCB subtype)[1] Concentration: 0.5 µM, 1 µM, 2 µM, 3 µM, 4 µM, 5 µM Incubation Time: 6 hours Result: Showed targeted downregulation of MCL-1 in both ABC and GCB subtypes.
[In Vivo]
Combination of Voruciclib hydrochloride (200 mpk; Oral gavage) and Venetoclax (10 mpk, 1 mpk, 50 mpk, 25 mpk in U2932, RIVA, SU-DHL-4 and NU-DHL-1, respectively) leads to enhance tumor growth inhibition compared to either drug alone in U2932, RIVA, SU-DHL-4 (six days per week for 4 weeks), and NU-DHL-1 models (five days per week for 3 weeks) of DLBCL[1]. Animal Model: ABC subtypes (U2932, RIVA, OCI-LY10), GCB subtypes (SU-DHL-4, NU-DHL-1) xenografted in Female NOD.CB17-Prkdcscid/NCrHsd mice Dosage: 200 mpk Administration: Oral gavage; U2932, RIVA, SU-DHL-4 (six days per week for 4 weeks), OCI-LY10 (six days per week for 2 weeks), NU-DHL-1 (five days per week for 3 weeks) Result: Combination with Venetoclax enhanced tumor growth inhibition in U2932, RIVA, SU-DHL-4 and NU-DHL-1 models except in OCI-LY10 model.
[References]