Brief Description

Dinaciclib (SCH727965) is a novel and potent CDK inhibitor for CDK2, CDK5, CDK1 and CDK9 with IC50 of 1 nM, 1 nM, 3 nM and 4 nM, respectively.
IC50 Value: 1 nM (CDK2); 1 nM(CDK5); 3 nM(CDK1); 4 nM(CDK9)
Target: CDK2/5/1/9
in vitro: Dinaciclib is a potent DNA replication inhibitor that blocks thymidine (dThd) DNA incorporation in A2780 cells with IC50 of 4 nM. Dinaciclib inhibits melanoma cell proliferation, and drives melanoma cells into massive apoptosis. Dinaciclib induces the apoptosis of several osteosarcoma cell lines including those resistant to doxorubicin and dasatinib. Dinaciclib attenuates the phosphorylation of RNAP II at serine 2 and the phosphorylation of the CDK inhibitor p27Kip1 at threonine 187. Reductions in phosphorylation activity occurrs at 12 - 40 nM Dinaciclib (4 to 16 hours post-Dinaciclib addition). Dinaciclib also reduces the phosphorylation of Rb at serine 807/811. Dinaciclib induces the apoptosis of mock- and p53-depleted U2OS cells to a similar extent.
in vivo: Dinaciclib i.p. administration at 8, 16, 32, and 48 mg/kg daily for 10 days results in tumor inhibition by 70%, 70%, 89%, and 96%, respectively. Dinaciclib MED (minimum effective dose) appears to be <8 mg/kg. Dinaciclib is well tolerated, and the maximum body weight loss in the highest dosage group is 5%. Dinaciclib has dose-dependent antitumor activity in vivo, and that nearly complete inhibition of tumor growth occurs at a dose level below the MTD (maximum tolerated dose). Dinaciclib has a short plasma half-life in mouse.

Solubility

DMSO

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

Light brown to brown solid