Voruciclib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的、选择性的、口服生物可利用的 CDK9 抑制剂，对于 CDK9/cyclinT2 和 CDK9/cyclinT1 的 Ki 值分别为 0.63 nM 和 1.68 nM。

A potent, selective and orally bioavailable CDK9 inhibitor with Ki of 0.63 nM and 1.68 nM for CDK9/cyclinT2 and CDK9/cyclinT1, respectively; also inhibits CDK6/cyclin D1, CDK4/cyclin D1, CDK1/cyclin B and CDK1/cyclin A with Ki of 3-10 nM, shows weak activity against MAK and ICK (Ki>250 nM); exhibits more selective target profile than flavopiridol, represses MCL-1 protein expression in preclinical models of DLBCL, causes tumor cell apoptosis and tumor growth inhibition combined with venetoclax in vivo.Blood Cancer Phase 1 Clinical.

Voruciclib (0.5-5 μM; 6 hours) shows targeted downregulation of MCL-1 in both ABC and GCB subtypes.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. Cell Viability Assay 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 down regulation of MCL-1 in both ABC and GCB subtypes.

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. 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.

P 1446 | P 1446A

Cell Cycle/DNA Damage

CDK

CDK

Cancer

Blood cancer

1000023-04-0

469.841

C22H19ClF3NO5

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (106.42 mM)

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

2-[2-Chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methyl-3-pyrrolidinyl]-4H-1-benzopyran-4-one

(-20℃)

With Ice Pack

≥ 2 years