オラパリブ 化学特性,用途語,生産方法
効能
抗悪性腫瘍薬, PARP阻害薬
商品名
リムパーザ (アストラゼネカ)
説明
Olaparib, marketed by AstraZeneca under the brand name Lynparza
, was approved in the USA in December 2014 as a targeted,
single-agent therapy for the treatment of germline BRCA-mediated
advanced ovarian cancer.Olaparib, originally developed by
KuDOS pharmaceuticals and later by AstraZeneca, functions as a
poly ADP ribose polymerase inhibitor and has been specifically
approved for patients who have received three or more treatments
of chemotherapy. In clinical trials, the drug prolonged progression-
free survival for patients suffering from platinum-sensitive
recurrent serous ovarian cancer. Olaparib is also currently in various phases of investigation for treatment of breast,
gastric, prostate, pancreatic and non-small cell lung cancer.
化学的特性
White Solid
使用
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.
定義
ChEBI: Olaparib is a member of the class of N-acylpiperazines obtained by formal condensation of the carboxy group of 2-fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid with the free amino group of N-(cyclpropylcarbonyl)piperazine; used to treat advanced ovarian cancer. It has a role as an antineoplastic agent, an EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor and an apoptosis inducer. It is a N-acylpiperazine, a member of cyclopropanes, a member of monofluorobenzenes and a member of phthalazines.
生物活性
Many of the products generated by alkylating agents on DNA can be efficiently repaired by normal base excision repair (BER). Some poly(ADP-ribose) polymerases (PARPs) assist in the repair of single-strand DNA nicks, an important step in BER. Olaparib is a potent inhibitor of PARP1 and PARP2 (IC50 = 5 and 1 nM, respectively) but is less effective against the PARP tankyrase-1 (IC50 = 1.5 μM). It can be used in cells and in animals, alone or in combination therapy with alkylating agents, to block BER and increase cancer cell death.[Cayman Chemical]
Mode of action
Olaparib is a small molecule inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential chemosensitizing, radiosensitizing, and antineoplastic activities. Olaparib selectively binds to and inhibits PARP, inhibiting PARP-mediated repair of single strand DNA breaks; PARP inhibition may enhance the cytotoxicity of DNA-damaging agents and may reverse tumor cell chemoresistance and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins and can be activated by single-stranded DNA breaks.
オラパリブ 上流と下流の製品情報
原材料
準備製品