Voruciclib

Cas No.:	1000023-04-0
Chemical Name:	2-(2-Chloro-4-(trifluoromethyl)phenyl)-5,7-dihydroxy-8-((2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-4H-1-benzopyran-4-one
Synonyms:	P1446A05, P1446A-05, P1446A 05, Voruciclib
SMILES:	O=C1C=C(C2=CC=C(C(F)(F)F)C=C2Cl)OC3=C([C@H]4[C@H](CO)N(C)CC4)C(O)=CC(O)=C13
Formula:	C22H19ClF3NO5
M.Wt:	469.84
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Voruciclib is a clinical stage orally active and selective CDK inhibitor with Ki values of 0.626 nM-9.1 nM. Voruciclib potently blocks CDK9, the transcriptional regulator of MCL-1. Voruciclib represses expression of MCL-1 in multiple models of diffuse large B-cell lymphoma (DLBCL)[1].
Target:	CDK9/cyc T2:0.626 nM (IC50) CDK9/CycT1:1.68 nM (IC50) CDK6/cycD1:2.92 nM (IC50) CDK4/Cyc D1:3.96 nM (IC50) CDK1/cycB:5.4 nM (IC50) CDK1/cyc A:9.1 nM (IC50)
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: 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.
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.