PHA-793887

A potent inhibitor of CDK2/5/7 with IC50 of 8/5/10 nM respectively; >6-fold less potency on CDK1/4/7; shows good efficacy in the human ovarian A2780, colon HCT-116 and pancreatic BX-PC3 carcinoma xenograft models; suitable for intravenous dosing. (In Vitro) :PHA-793887 partially inhibits Rb phosphorylation at 1 μM and almost completely at 3 μM, in A2780 tumor cell line. PHA-793887 (1 μM) partially inhibits phosphorylation of the Cdk2 substrates Rb and NPM in A2780 tumor cell line. PHA-793887 (6 μM) significantly inhibits Rb and NPM phosphorylation in MCF7 cell line. PHA-793887 shows cytotoxic activities against leukemic cell lines in vitro, with IC50 ranging from 0.3 to 7 μM. In colony assays, PHA-793887 is highly cytotoxic for leukemia cell lines, with an IC50 <0.1 μM. PHA-793887 induces cell-cycle arrest, inhibits Rb and nucleophosmin phosphorylation, and modulates cyclin E and cdc6 expression at low doses of 0.2 to 1 μM and induces apoptosis at the highest dose of 5 μM. PHA-793887 is a novel inhibitor of several cdk, including cdk1, cdk2, cdk4, cdk5, cdk7, and cdk9 with IC50 in the 5 to 140 nM range. (In Vivo) :PHA-793887 induces tumor growth inhibition in the range of 50% at dose of 15 mg/kg to 75% at dose of 30 mg/kg in CD-1 nude mice. PHA-793887 (30 mg/kg, i.v.) also induces significant downregulation of the 58-gene panel in the skin of CD-1 mice. PHA-793887 (20 mg/kg, i.v.) induces tumor regression in the HL60 model. In the K562 model, PHA-793887 significantly reduces tumor growth. Moreover, PHA-793887 (20 mg/kg, i.v.) inhibits human primary leukemia growth in engraftment setting in vivo.

718630-59-2

PHA 793887 | PHA793887

Metabolism Research

>98% (HPLC)

10 mM in DMSO

CC (C) CC (=O) NC1=NNC2=C1CN (C (=O) C1CCN (C) CC1) C2 (C) C

C19H31N5O2

361.4818

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.