產品名稱：Olaparib
產品貨號：LC  O-9201 
產品規格：100 MG
Olaparib is a poly(ADP-ribose) polymerase 1 (PARP1) inhibitor and an anti-cancer drug being tested in patients with mutations in the genes BRCA1 or BRCA2.
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).
Other CAS numbers previously assigned to olaparib, namely 894104-70-2, 937799-91-2, and 1021843-02-6, have been deleted by CAS and are no longer in use.
Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO at 33 mg/mL; soluble in ethanol at 1.7 mg/mL with slight warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 µM buffers, serum, or other additives may increase or decrease the aqueous solubility.  Disposal:  A

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