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Article ｜ 22 Mar 2024
WIKIMOLE—Olaparib
By TargetMol
Olaparib, catalog number T3015, also known as AZD2281 or KU0059436, is a small molecule inhibitor of PARP1/PARP2. It exhibits selectivity and oral activity. Additionally, Olaparib also possesses activity in inducing autophagy and mitochondrial autophagy.
Note: PARP stands for poly (ADP-ribose) polymerase.
Mechanism of action
Olaparib, as a PARP inhibitor, can be used to treat specific types of cancer patients, such as breast cancer, ovarian cancer, etc. PARP is an enzyme that plays a crucial role in DNA repair, maintenance of genomic integrity, as well as various metabolic and signaling processes. PARP inhibitors work by blocking the activity of PARP enzyme, thereby limiting the ability of cancer cells to repair damaged DNA, leading to apoptosis of tumor cells.
Application
Olaparib, marketed under the brand name Lynparza?, is an approved PARP inhibitor used to treat ovarian cancer and breast cancer patients carrying BRCA mutations. For these patients, specific gene mutations like BRCA disrupt other DNA repair pathways, making them particularly sensitive to PARP inhibitors. Treating ovarian and breast cancer patients carrying BRCA mutations is a common application of PARP inhibitors. Additionally, PARP inhibitors have shown therapeutic potential in other cancer types and non-oncological diseases.
Approved PARP inhibitors on the market include Olaparib, Rucaparib, Niraparib, Talazoparib, etc.
Reference
[1] Prasad CB, Prasad SB, Yadav SS, Pandey LK, Singh S, Pradhan S, Narayan G. Olaparib modulates DNA repair efficiency, sensitizes cervical cancer cells to cisplatin and exhibits anti-metastatic property. Sci Rep. 2017 Oct 9;7(1):12876. doi: 10.1038/s41598-017-13232-3. PMID: 28993682; PMCID: PMC5634505.
[2] Pommier Y, O'Connor MJ, de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action [published correction appears in Sci Transl Med. 2016 Dec 7;8(368):368er7]. Sci Transl Med. 2016;8(362):362ps17. doi:10.1126/scitranslmed.aaf9246
[3] Long X, Dai A, Huang T, et al. Simultaneous Delivery of Dual Inhibitors of DNA Damage Repair Sensitizes Pancreatic Cancer Response to Irreversible Electroporation. ACS Nano. 2023;17(13):12915-12932. doi:10.1021/acsnano.3c05009
[4] Valentini E, Di Martile M, Brignone M, et al. Bcl-2 family inhibitors sensitize human cancer models to therapy. Cell Death Dis. 2023;14(7):441. Published 2023 Jul 17. doi:10.1038/s41419-023-05963-1
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