Atuveciclib

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

Atuveciclib (BAY-1143572) 是一种有效的、高选择性的、口服生物可利用的 CDK9/P-TEFb 抑制剂，对 CDK9/CyclinT1 的 IC50 为 6 nM。

Atuveciclib (BAY-1143572) is a potent, highly selective, orally bioavailable CDK9/P-TEFb inhibitor with IC50 of 6 nM for CDK9/CyclinT1; displays >150-fold selectivity over CDK1/2/3/5/6/7 (IC50>800 nM), also shows submicromolar inhibitory activity against GSK3α (IC50=45 nM), GSK3β (IC50=87?nM); demonstrates antiproliferative activity against HeLa cells (IC50=920 nM) and MOLM‐13 cells (IC50=310 nM); exhibits anticancer activity in human AML models.Blood Cancer Phase 1 Clinical.

Atuveciclib (BAY-1143572) inhibits the proliferation of 7 MLL-rearrangements positive and negative AML cell lines with a median IC50 of 385 nM (range 230-1100 nM) and induces apoptosis. Atuveciclib (BAY-1143572) has potent and highly selective PTEFb-kinase inhibitory activity in the low nanomolar range against PTEFb/CDK9 and an at least 50-fold selectivity against other CDKs. Atuveciclib (BAY-1143572) shows a favorable selectivity against a panel of non-CDK kinases. It shows broad antiproliferative activity against a panel of tumor cell lines with sub-micromolar IC50 values. The concentration-dependent inhibition of the phosphorylation of the RNA polymerase II and downstream reduction of MYC mRNA and protein levels is observed.

Atuveciclib (BAY-1143572) exhibits single agent efficacy at tolerated doses in 4 out of 5 AML xenograft tumor models in mice and in 2 out of 2 AML xenograft tumor models in rats upon once daily oral administration. Partial or even complete remissions could be achieved in several models.The inhibition of MYC mRNA is also observed in blood cells of Atuveciclib (BAY-1143572)-treated rats indicating the potential clinical utility of MYC in blood cells as a pharmacodynamic marker in clinical development. The in vivo efficacy of Atuveciclib (BAY-1143572) is significantly enhanced in combination with several chemotherapeutics in different solid tumor models.

BAY 1143572 | BAY1143572

Cell Cycle/DNA Damage

CDK

CDK

Cancer

Blood cancer

1414943-88-6

387.433

C18H18FN5O2S

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (258.11 mM)

O=S(C)(CC1=CC=CC(NC2=NC(C3=CC=C(F)C=C3OC)=NC=N2)=C1)=N

(3-((4-(4-fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino)benzyl)(imino)(methyl)-l6-sulfanone

(-20℃)

With Ice Pack

≥ 2 years