1000023-04-0

1000023-04-0 structure

Name: Voruciclib
Chemical Name: 2-[2-chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one
CAS Number: 1000023-04-0
Molecular Formula: C₂₂H₁₉ClF₃NO₅
Molecular Weight: 469.83800
Catalog: Signaling Pathways Cell Cycle/DNA Damage CDK
Create Date: 2017-09-29 10:25:44
Modify Date: 2024-01-10 15:02:15
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].

Name	2-[2-chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one
Synonyms	UNII-W66XP666AM Voruciclib

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].
Related Catalog	Research Areas >> Cancer Signaling Pathways >> Cell Cycle/DNA Damage >> CDK
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 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.
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.
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.

Molecular Formula	C₂₂H₁₉ClF₃NO₅
Molecular Weight	469.83800
Exact Mass	469.09000
PSA	94.14000
LogP	4.26130