Uses
PHA-793887 is a potent CDK (cyclin-dependent kinase) inhibitor. Recent studies shows that PHA-793887 has promising therapeutic activity against acute leukemias in vitro and in vivo. PHA-793887 was used to successfully modulate E2F transcriptional factor-dependent cell cycle, DNA replication, mitosis and apoptosis related gene in both tumors and skin biopsy from patients with solid tumors.
Definition
ChEBI: N-[6,6-dimethyl-5-[(1-methyl-4-piperidinyl)-oxomethyl]-1,4-dihydropyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide is a piperidinecarboxamide.
Biological Activity
PHA-793887 is a highly potent and selective pan-CDK inhibitor (CDK1/2//4/5/7/9 IC50 5-140 nM; IC50 >10 μM against 34 other kinases) with anti-proliferative activity against several solid tumor cell lines (IC50 <1 μM) by blocking Rb phosphorylation and the expression of S-phase cyclinssuch as cyclin A. PHA-793887 exhibits in vivo anti-leukemia efficacy in murine xenograft models (20 mg/kg via daily i.v.; HL60K562ALL-2 or AML-PS).
Enzyme inhibitor
This cyclin kinase-directed inhibitor (FW = 361.48 g/mol; CAS 718630-59-
2, 718630-60-5 (HCl); Solubility: 70 mg/mL DMSO; <1 mg/mL Water;
Formulation: Dissolve in 5% dextrose solution), also known as N- (6,6-
dimethyl-5- (1-methylpiperidine-4-carbonyl) -1,4,5,6-tetrahydropyrrolo[3,4-
c]pyrazol-3-yl) -3-methylbutanamide, targets CDK2, CDK5 and CDK7 with
IC50 values of 8 nM, 5 nM and 10 nM, respectively. Alternative target:
glycogen synthase-3 kinase-β (GSK-3β). Cyclin Target Selectivity: Cdk1
(weak, if any), Cdk2 (+++), Cdk3 (weak, if any), Cdk4 (weak, if any), Cdk5
(+++), Cdk6 (weak, if any), Cdk7 (+++), Cdk8 (weak, if any), Cdk9 (weak,
if any), Cdk10 (weak, if any).
