85-1693-55　Olaparib 25mg　CAS No:763113-22-0　018732

特徴

• Olaparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor. Olaparib has been shown to induce significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Recent studies show that Olaparib increases radiosensitivity of a lung tumor xenograft, making it a potential candidate for use in combination with radiotherapy
• PARP1 acts as a critical molecule in the repair of DNA single-strand breaks (SSBs) and plays an important role in maintaining DNA integrity. de Murcia, J., et al. "Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells." Proc. Natl. Acad. Sci. USA 94: 7303-7307 (1997)
• PARP inhibitors inhibit PARP1 during S-phase and induce inactivation of SSB repair and thus cause DNA double-strand breaks, which induces BRCA-deficient cancer cell apoptosis. Bryant, H.E., et al. "Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase." Nature 434: 913-917 (2005). Farmer, H., et al. "Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy." Nature 434: 917-921 (2005)
• The PARP inhibitor olaparib was tested in a genetically engineered mouse model for BRCA1-associated breast cancer. Olaparib inhibited tumor growth and significantly improved survival without signs of toxicity. Rottenberg, S., et al. "High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs." Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008)
• Long-term treatment with olaparib caused the development of drug resistance, which was induced by up-regulation of Abcb1a/b genes encoding P-glycoprotein efflux pumps. The resistance to olaparib could be overcome by tariquidar, a P-glycoprotein inhibitor. Rottenberg, S., et al. "High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs." Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008)
• Combination treatment using olaparib with cisplatin or carboplatin improved the recurrence-free and overall survival in a murine model, indicating that olaparib enhances the effect of these DNA-damaging agents. Rottenberg, S., et al. "High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs." Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008)
• Olaparib inhibited the growth of BRCA2-deficient versus BRCA2-proficient mammary tumor cells. Combination treatment of olaparib and cisplatin had a synergistic cytotoxicity against BRCA2-deficient cells but not against BRCA2-proficient control cells. Evers, B., et al. "Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin." Clin. Cancer Res. 14: 3916-3925 (2008).
• Synonyms:4-[[3-[[4-(Cyclopropylcarbonyl)-1-piperazinyl]carbonyl]-4-fluorophenyl]methyl]-1(2H)-phthalazinone; AZD-2281; KU 0059436; KU-59436; 1-(Cyclopropylcarbonyl)-4-[5-[(3,4-dihydro-4-oxo-1-phthalazinyl)methyl]-2-fluorobenzoyl]piperazine
• Molecular Formula:C₂₄H₂₃FN₄O₃
• Molecular Weight:434.46
• Appearance:Supplied as a white to off-white, cystalline or powder
• Purity:≥99% (HPLC, TLC)
• Solubility:Soluble in DMSO at 33mg/ml; soluble in ethanol at 1.7mg/ml with slight warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20uM buffers, serum, or other additives may increase or decrease the aqueous solubility.
• Melting Point:208-209ºC
• Elemental Analysis:Calculated:%C: 66.35%%H: 5.34%%F: 4.37%%N: 12.90%
• Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 6 months after receipt at -20°C. Reconstitute with DMSO. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
• Important Note:This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications without the expressed written authorization of United States Biological.
• Toxicity and Hazards: All products should be handled by qualified personnel only, trained in laboratory procedures.