PHA-793887

SKU: orb1224155

Description

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.

Research Area

Metabolism Research

Key Properties

• CAS Number: 718630-59-2
• MW: 361.4818
• Purity: >98% (HPLC)
• Formula: C₁₉H₃₁N₅O₂
• SMILES: CC(C)CC(=O)NC1=NNC2=C1CN(C(=O)C1CCN(C)CC1)C2(C)C
• Target: CDK
• Solubility: 10 mM in DMSO

Bioactivity

• 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.
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• 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.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PHA 793887 | PHA793887

Quick Database Links

Gene Symbol

CDK