Olaparib.

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Bochum S, Berger S, Martens UM

Olaparib.

Recent Results Cancer Res. 2018;211:217-233. doi: 10.1007/978-3-319-91442-8_15.

PubMed ID

30069770 [ View in PubMed

]

Abstract

Olaparib (Lynparza [AstraZeneca, Cambridge, UK], formerly referred to as AZD2281 or KU0059436) is an oral poly(ADP-ribose) polymerase (PARP) inhibitor. It is rationally designed to act as a competitive inhibitor of NAD(+) at the catalytic site of PARP1 and PARP2, both members of the PARP family of enzymes that are central to the repair of DNA single-strand breaks (SSBs) mediated via the base excision repair (BER) pathway. Inhibition of the BER pathway by olaparib leads to the accumulation of unrepaired SSBs, which leads to the formation of deleterious double-strand breaks (DSBs). In cells with an intact homologous recombination (HR) pathway, these DSBs can be repaired effectively. However, in tumors with homologous recombination repair deficiencies, olaparib causes synthetic lethality through the combination of two molecular events that are otherwise nonlethal when occurring in isolation. Olaparib is already approved for the treatment of patients with recurrent ovarian cancer and a BRCA mutation, and it has been shown to provide clinically meaningful benefits among such patients. It has also shown promising activity in patients with metastatic breast or prostate cancer and a germline BRCA mutation. Besides its usage as a single agent, olaparib can also act either as a chemo- and/or radiosensitizer, due to its ability to potentiate the cytotoxic effects of these therapeutic agents. However, a clear patient benefit for the latter application has not been demonstrated yet.

DrugBank Data that Cites this Article

Drugs

Olaparib

Talazoparib

Niraparib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Olaparib	Poly [ADP-ribose] polymerase 1	Protein	Humans	Yes	Inhibitor	Details
Olaparib	Poly [ADP-ribose] polymerase 2	Protein	Humans	Yes	Inhibitor	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Olaparib	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Olaparib Clozapine	The metabolism of Olaparib can be decreased when combined with Clozapine.
Olaparib Diltiazem	The metabolism of Olaparib can be decreased when combined with Diltiazem.
Olaparib Verapamil	The metabolism of Olaparib can be decreased when combined with Verapamil.
Olaparib Simeprevir	The metabolism of Olaparib can be decreased when combined with Simeprevir.
Olaparib Venetoclax	The metabolism of Olaparib can be decreased when combined with Venetoclax.