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: Enhanced tumor growth inhibition in U2932, RIVA, SU-DHL-4 and NU-DHL-1 models except in OCI-LY10 model.
In Vitro
Voruciclib (0.5-5 µM; 6 hours) shows targeted downregulation of MCL-1 in both ABC and GCB subtypes[1]. Cell Viability Assay[1] Cell Line: U2932, RIVA, OCI-LY10 cells (ABC subtype), NU-DHL-1, SU-DHL-4, SU-DHL-6 cells (GCB subtype) 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.
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Dey J, et al. Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition. Sci Rep. 2017 Dec 21;7(1):18007.
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