85-4640-80　Purvalanol A, Free Base, 99+% 50mg　CAS No:212844-53-6　368499

特徴

• Purvalanol A is a cell-permeable, potent, and selective cyclin-dependent kinase (CDK) inhibitor. It inhibited CDK kinases with IC50 values of 4 nM for CDC2/cyclin B, 70 nM for CDK2/cyclin A, 35 nM for CDK2/cyclin E, 75 nM for CDK5/p35, and 850 nM for CDK4/cyclin D1. Gray N.S., et al. “Exploiting chemical libraries, structure and genomics in the search for kinase inhibitors.” Science 281: 533-538 (1998)
• Purvalanol A inhibited radiation-induced CDC2 kinase activity and induced apoptosis by increasing the levels of active fragments of caspase 3. Lizuka D., et al. “Purvalanol A enhances cell killing by inhibiting up-regulation of CDC2 kinase activity in tumor cells irradiated with high doses of X rays.” Radiat. Res. 167: 563-571 (2007)
• Purvalanol A prevented hippocampal proliferation in a time- and concentration -dependent manner. Mackowiak M., et al. “Purvalanol A, inhibitor of cyclin-dependent kinases attenuates proliferation of cells in the dentate gyrus of the adult rat hippocampus.” Pharmacol. Rep. 57: 845-849 (2005)Purvalanol A arrested cells at the G(2)-M phase and induced apoptosis in a concentration-dependent manner. It also concomitantly down-regulated the antiapoptotic protein survivin, a member of the inhibitors of apoptosis protein family. Pennati M., et al. “Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation.” Mol. Cancer Ther. 4: 1328-1337 (2005)
• In synchronized cells, purvalanol A arrested cells in the G1 and G2 phases, but did not prevent DNA synthesis in S-phase cells. After mouse fibroblasts and human cancer cell lines were incubated with purvalanol A for 24 hr, inhibition of cell proliferation and cell death were observed. Villerbu N., et al. “Cellular effects of purvalanol A: a specific inhibitor of cyclin-dependent kinase activities.” Int. J. Cancer 97: 761-769 (2002).
• PD 0332991 is a potent selective inhibitor of cyclin dependent kinases CDK4 and CDK6 with in vitro IC50 = 11 nM (CDK4) and 16 nM (CDK6). PD 0332991 induces G1 arrest in retinoblastoma (Rb)-positive tumor cells.
• Palbociclib, also known as PD 0332991, is an inhibitor of cyclin-dependent kinases (CDK)4 and CDK6. It inhibited CDK4 and CDK6 with IC50 values of 11 nM and 16 nM, respectively. It inhibited the proliferation of retinoblastoma (Rb)-positive tumor cells in vitro with IC50 values ranging from 40 to 400 nM and induced a G1 arrest with a concomitant reduction of phospho-Ser780/Ser795 on the Rb protein. It also had antitumor activity against a panel of advanced stage human tumor xenografts in vivo. Fry D.W., et al. "Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts." Mol. Cancer Ther. 3: 1427-1438 (2004).
• Palbociclib potently inhibited the phosphorylation of the Rb protein and cell cycle progression through G1 in primary 5T33MM cells in vivo and ex vivo. It induced tumor suppression and a significant improvement in survival of 5T33MM diseased mice. Palbociclib sensitized 5T33MM tumor cells to killing by bortezomib in vitro and prolonged survival in vivo. Menu E., et al. "A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model." Cancer Res. 68: 5519-5523 (2008)
• CDK4/6 inhibition by palbociclib induced a cooperative cytostatic effect in combination with doxorubicin in triple-negative breast cancer (TNBC) cells but ultimately antagonized cytotoxicity. However, palbociclib did not modify the sensitivity of Rb-deficient TNBC cells to doxorubicin-mediated cytotoxic chemotherapy. Palbociclib antagonized doxorubicin-mediated cytotoxicity in vivo in an Rb-dependent manner and allowed tumor cell outgrowth following doxorubicin treatment. McClendon A.K., et al. "CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy." Cell Cycle 11: 2747-2755 (2012).
• Appearance:Pale green, cystalline powder
• Purity:≥99% (HPLC, TLC)
• Melting Point:154-156.5°C
• Solubility:DMSO
• Method for Determining Identity:NMR (DMSO-d6) and MS
• Storage and Stability:May be stored at RT for short-term only. Long-term storage is recommended at -20°C. For maximum recovery of product, centrifuge the original vial prior to removing the cap