BAY-1143572

Cas No.:	1414943-88-6
Synonyms:	BAY1143572; BAY 114357
SMILES:	N=S(CC1=CC(NC2=NC(C3=CC=C(F)C=C3OC)=NC=N2)=CC=C1)(C)=O
Formula:	C18H18FN5O2S
M.Wt:	387.43
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:

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. 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. 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.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 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 BAY 1143572 is significantly enhanced in combination with several chemotherapeutics in different solid tumor models.