Brief Description

PHA-848125(Milciclib) is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM; >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7.
IC50 Value: 45 nM
Target: CDK2
in vitro: PHA-848125 inhibits, although with lower potency, the activities of cyclin H/CDK7, cyclin D1/CDK4, p35/CDK5, as well as cyclin E/CDK2 and cyclin B/CDK1 with IC50 values of 0.15, 0.16, 0.265, 0.363, 0.398 μM, respectively. PHA-848125 also impairs phosphorylation of the retinoblastoma protein at CDK2 and CDK4 specific sites, reduces retinoblastoma protein and cyclin A levels, and increases p21(Cip1), p27(Kip1) and p53 expression. PHA-848125 is added to the cells 48 h after TMZ and cell growth is evaluated after 3 additional days of culture. A drug combination of TMZ, BG and PHA-848125 induces an additive or synergistic effect on cell growth, depending on the cell line.
in vivo: In the preclinical xenograft A2780 human ovarian carcinoma model, PHA-848125 reveals good efficacy and is well tolerated upon repeated daily treatments. Treatment of K-Ras(G12D)LA2 mice with PHA-848125 (40 mg/kg twice daily for 10 days) results in significant tumor growth inhibition at the end of the treatment and is accompanied by a reduction in the cell membrane turnover. On the other hand, following oral administration, PHA-848125 shows significant antitumor activity in various human xenografts, carcinogen-induced tumors and in disseminated primary leukemia models; the plasma concentrations in rodents being in the same range as those found inhibiting cancer cell proliferation.

Solubility

DMSO 90 mg/mL; Water <1 mg/mL

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

Light yellow to yellow solid