Olaparib | AZD-2281 | CAS#763113-22-0 | PARP inhibitor

MedKoo Cat#: 200422 | Name: Olaparib (AZD-2281)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Olaparib, also known as AZD-2281 or KU-59436 , 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. Olaparib was approved in 2014 for treating advanced ovarian cancer.

Chemical Structure

Olaparib (AZD-2281)

CAS#763113-22-0

Theoretical Analysis

MedKoo Cat#: 200422

Name: Olaparib (AZD-2281)

CAS#: 763113-22-0

Chemical Formula: C24H23FN4O3

Exact Mass: 434.1754

Molecular Weight: 434.46

Elemental Analysis: C, 66.35; H, 5.34; F, 4.37; N, 12.90; O, 11.05

Price and Availability

Size	Price	Availability
200mg	USD 90.00	Ready to ship
500mg	USD 150.00	Ready to ship
1g	USD 250.00	Ready to ship
2g	USD 450.00	Ready to ship
5g	USD 950.00	Ready to ship
10g	USD 1,650.00	Ready to ship

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Related CAS #

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Synonym

AZD2281; AZD-2281; AZD 2281; KU59436; KU-59436; KU 59436; KU0059436; KU-0059436; KU 0059436; Olaparib. trade name Lynparza.

IUPAC/Chemical Name

4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one

InChi Key

FDLYAMZZIXQODN-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H23FN4O3/c25-20-8-5-15(14-21-17-3-1-2-4-18(17)22(30)27-26-21)13-19(20)24(32)29-11-9-28(10-12-29)23(31)16-6-7-16/h1-5,8,13,16H,6-7,9-12,14H2,(H,27,30)

SMILES Code

O=C1NN=C(CC2=CC=C(F)C(C(N3CCN(C(C4CC4)=O)CC3)=O)=C2)C5=C1C=CC=C5

Appearance

white solid powder

Purity

>99% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Olaparib (AZD-2281, trade name Lynparza) is an FDA-approved chemotherapeutic agent, developed by KuDOS Pharmaceuticals and later by AstraZeneca. It is an inhibitor of poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair.[1] It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which includes many ovarian, breast, and prostate cancers. Early Phase I trials were promising, and olaparib underwent Phase II trials. However, in December 2011, AstraZeneca announced following interim analysis of a phase-II study which indicated that the previously reported progression free survival benefit was unlikely to translate into an overall survival benefit, that it would not progress into Phase III development for the maintenance treatment of serous ovarian cancer, and took a charge of $285 million. The decision to discontinue development of the drug was reversed in 2013, with AstraZeneca posting a new Phase III trial of Olaparib for patients with BRCA mutated ovarian cancer in April 2013. On December 19, 2014, the FDA approved olaparib as monotherapy (at 400 mg taken twice per day) for patients with germline BRCA mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. (source: http://en.wikipedia.org/wiki/Olaparib).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T05K21

QC Data

View QC data: current batch, Lot#A8T05K21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Olaparib (AZD2281; KU0059436) is a PARP inhibitor with IC50s of 5 and 1 nM for PARP1 and PARP2, respectively.

In vitro activity:

In HPDE cells subjected to oxidative stress, olaparib inhibited PARylation (as measured by the quantification of poly(ADP-ribose) [PAR], the product of the enzyme) already at the lowest concentration (1 μM) used, confirming the well-established potent inhibitory effect of olaparib on PARP1 catalytic activity in this cell line (Fig. 8). PARP1 enzyme levels were downregulated by the oxidative stress challenge; this downregulation was also partially attenuated by the lower concentrations (1–3 μM) of olaparib (Fig. 8). In line with prior findings demonstrating that PARP inhibition prevents the cellular depletion of its substrate, NAD+, olaparib also protected against the H2O2-induced loss of cellular NAD+ levels, with the effects already near-maximal at its lowest concentration tested (1 μM) (Fig. 9). Reference: Shock. 2020 May; 53(5): 653–665. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944774/

In vivo activity:

In young adult male mice subjected to CLP, olaparib (1, 3 or 10 mg/kg i.p.) concentration-dependently improved several parameters of multiorgan dysfunction (Figs. 1–3). For instance, the CLP-induced increases in spleen MPO content and liver and spleen MDA levels were attenuated by olaparib (Fig. 1). In addition, the CLP-induced increases in plasma markers of liver and pancreas injury (ALP, ALT, amylase) and renal dysfunction (BUN) were attenuated by olaparib treatment (Fig. 2). The histopathological pictures of the lungs did not show marked alterations in any of the groups, with slight emphysema evident in all CLP groups (Fig. 3). In the liver, foamy degeneration of numerous hepatocytes is evident in the CLP group; olaparib, at the 10 mg/kg dose, normalized the morphology of the hepatocytes (Fig. 4). In the spleen, CLP induced macrophage infiltration, and evidence of hemolysis was evident, with no marked differences between CLP groups with or without olaparib (Fig. 5). Reference: Pharmacol Res. 2019 Jul; 145: 104263. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662650/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	23.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 434.46 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Ahmad A, Haas De Mello A, Szczesny B, Törö G, Marcatti M, Druzhyna N, Liaudet L, Tarantini S, Salomao R, Garcia Soriano F, Szabo C. Effects of the Poly(ADP-Ribose) Polymerase Inhibitor Olaparib in Cerulein-Induced Pancreatitis. Shock. 2020 May;53(5):653-665. doi: 10.1097/SHK.0000000000001402. PMID: 31274831; PMCID: PMC6944774. 2. Bianchi A, Lopez S, Altwerger G, Bellone S, Bonazzoli E, Zammataro L, Manzano A, Manara P, Perrone E, Zeybek B, Han C, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Newberg JY, Pavlick DC, Elvin J, Frampton GM, Schwartz PE, Santin AD. PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib. Gynecol Oncol. 2019 Oct;155(1):144-150. doi: 10.1016/j.ygyno.2019.08.010. Epub 2019 Aug 18. PMID: 31434613; PMCID: PMC6788971. 3. Gu Z, Wang L, Yao X, Long Q, Lee K, Li J, Yue D, Yang S, Liu Y, Li N, Li Y. ClC-3/SGK1 regulatory axis enhances the olaparib-induced antitumor effect in human stomach adenocarcinoma. Cell Death Dis. 2020 Oct 22;11(10):898. doi: 10.1038/s41419-020-03107-3. PMID: 33093458; PMCID: PMC7583252. 4. Ahmad A, Vieira JC, de Mello AH, de Lima TM, Ariga SK, Barbeiro DF, Barbeiro HV, Szczesny B, Törö G, Druzhyna N, Randi EB, Marcatti M, Toliver-Kinsky T, Kiss A, Liaudet L, Salomao R, Soriano FG, Szabo C. The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity for repurposing a clinically used oncological drug for the experimental therapy of sepsis. Pharmacol Res. 2019 Jul;145:104263. doi: 10.1016/j.phrs.2019.104263. Epub 2019 May 6. PMID: 31071432; PMCID: PMC6662650.

In vitro protocol:

In vivo protocol:

1. Gu Z, Wang L, Yao X, Long Q, Lee K, Li J, Yue D, Yang S, Liu Y, Li N, Li Y. ClC-3/SGK1 regulatory axis enhances the olaparib-induced antitumor effect in human stomach adenocarcinoma. Cell Death Dis. 2020 Oct 22;11(10):898. doi: 10.1038/s41419-020-03107-3. PMID: 33093458; PMCID: PMC7583252. 2. Ahmad A, Vieira JC, de Mello AH, de Lima TM, Ariga SK, Barbeiro DF, Barbeiro HV, Szczesny B, Törö G, Druzhyna N, Randi EB, Marcatti M, Toliver-Kinsky T, Kiss A, Liaudet L, Salomao R, Soriano FG, Szabo C. The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity for repurposing a clinically used oncological drug for the experimental therapy of sepsis. Pharmacol Res. 2019 Jul;145:104263. doi: 10.1016/j.phrs.2019.104263. Epub 2019 May 6. PMID: 31071432; PMCID: PMC6662650.

1: Moniot A, Schneider C, Chardin L, Yaniz-Galende E, Genestie C, Etiennot M, Henry A, Drelon C, Le Formal A, Langlois B, Venat L, Louvet C, Favier L, Lortholary A, Berton-Rigaud D, Dohollou N, Desauw C, Fabbro M, Malaurie E, Dubot C, Kurtz JE, Bonichon Lamichhane N, Pujade-Lauraine É, Jeanne A, Leary A, Dedieu S. The CD47/TSP-1 axis: a promising avenue for ovarian cancer treatment and biomarker research. Mol Cancer. 2024 Aug 14;23(1):166. doi: 10.1186/s12943-024-02073-0. PMID: 39138571. 2: Kulkarni S, Gajjar K, Madhusudan S. Poly (ADP-ribose) polymerase inhibitor therapy and mechanisms of resistance in epithelial ovarian cancer. Front Oncol. 2024 Jul 29;14:1414112. doi: 10.3389/fonc.2024.1414112. PMID: 39135999; PMCID: PMC11317305. 3: Liu Y, Zhu J, Zhou S, Hou Y, Yan Z, Ao X, Wang P, Zhou L, Chen H, Liang X, Guan H, Gao S, Xie D, Gu Y, Zhou PK. Low-dose ionizing radiation-induced RET/PTC1 rearrangement via the non-homologous end joining pathway to drive thyroid cancer. MedComm (2020). 2024 Aug 12;5(8):e690. doi: 10.1002/mco2.690. PMID: 39135916; PMCID: PMC11318340. 4: Fenton SE, Hussain M. Olaparib monotherapy or in combination with abiraterone for treating mutated metastatic castration-resistant prostate cancer: alone or stronger together? Expert Opin Investig Drugs. 2024 Aug 13. doi: 10.1080/13543784.2024.2391828. Epub ahead of print. PMID: 39135527. 5: Romaniuk-Drapala A, Skupin-Mrugalska P, Garbuzenko O, Hatefi A, Minko T. Synergistic antitumor effect of liposomal-based formulations of olaparib and topotecan in primary epithelial ovarian cancer cells. Cancer Cell Int. 2024 Aug 12;24(1):285. doi: 10.1186/s12935-024-03469-0. PMID: 39135053; PMCID: PMC11320834. 6: Kawamoto Y, Yamai T, Ikezawa K, Seiki Y, Watsuji K, Hirao T, Urabe M, Kai Y, Takada R, Mukai K, Nakabori T, Uehara H, Inoue T, Fujisawa F, Ohkawa K. Clinical significance of germline breast cancer susceptibility gene (gBRCA) testing and olaparib as maintenance therapy for patients with pancreatic cancer. BMC Cancer. 2024 Aug 12;24(1):1000. doi: 10.1186/s12885-024-12722-8. PMID: 39134950; PMCID: PMC11321060. 7: Yang C, Song X, Sun H, Chen X, Liu C, Chen M. Cardiovascular adverse events associated with PARP inhibitors for ovarian cancer: a real world study (RWS) with Bayesian disproportional analysis based on the FDA adverse event reporting system (FAERS). Expert Opin Drug Saf. 2024 Aug 12:1-8. doi: 10.1080/14740338.2024.2390640. Epub ahead of print. PMID: 39132853. 8: Almaraz-Postigo S, Sanz E, Pandiella A, Díaz-Rodríguez E. Ocoxin Oral Solution Triggers DNA Damage and Cell Death in Ovarian Cancer. Nutrients. 2024 Jul 25;16(15):2416. doi: 10.3390/nu16152416. PMID: 39125297; PMCID: PMC11313973. 9: Erratum: Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Aug 9:JCO2401660. doi: 10.1200/JCO-24-01660. Epub ahead of print. Erratum for: J Clin Oncol. 2024 Jan 20;42(3):283-299. doi: 10.1200/JCO.23.02132. PMID: 39121439. 10: Alés-Martínez JE, Balmaña J, Sánchez-Rovira P, Salvador Bofill FJ, García Sáenz JÁ, Pimentel I, Morales S, Fernández-Abad M, Lahuerta Martínez A, Ferrer N, Zamora P, Bermejo B, Díaz-Redondo T, López-Ceballos MH, Galán M, Pérez- Escuredo J, Calabuig L, Sampayo M, Pérez-Garcia JM, Cortés J, Llombart-Cussac A. Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study. Breast. 2024 Aug 2;77:103780. doi: 10.1016/j.breast.2024.103780. Epub ahead of print. PMID: 39116683. 11: Hussain M, Kocherginsky M, Agarwal N, Adra N, Zhang J, Paller CJ, Picus J, Reichert ZR, Szmulewitz RZ, Tagawa ST, Kuzel TM, Bazzi LA, Daignault-Newton S, Whang YE, Dreicer R, Stephenson RD, Rettig MB, Shevrin D, Gerke T, Chinnaiyan AM, Antonarakis ES. Abiraterone, Olaparib, or Abiraterone + Olaparib in First- line Metastatic Castration-Resistant Prostate Cancer with DNA Repair Defects (BRCAAway). Clin Cancer Res. 2024 Aug 8. doi: 10.1158/1078-0432.CCR-24-1402. Epub ahead of print. PMID: 39115414. 12: Barros AG, Mansinho H, Couto N, Teixeira MR, Tonin FS, Francisco R, Duarte- Ramos F. The Initial Journey of Patients with Metastatic Pancreatic Cancer (PaCTO Project): A Nationwide Survey among Portuguese Specialist Physicians. GE Port J Gastroenterol. 2023 Sep 5;31(4):262-272. doi: 10.1159/000533178. PMID: 39114325; PMCID: PMC11305690. 13: Shin YB, Choi JY, Yoon MS, Yoo MK, Shin DH, Lee JW. Evaluation of Anticancer Efficacy of D-α-Tocopheryl Polyethylene-Glycol Succinate and Soluplus® Mixed Micelles Loaded with Olaparib and Rapamycin Against Ovarian Cancer. Int J Nanomedicine. 2024 Aug 2;19:7871-7893. doi: 10.2147/IJN.S468935. PMID: 39114180; PMCID: PMC11304412. 14: Bhandari SK, Wiest N, Sallmyr A, Du R, Tomkinson AE. Redundant but essential functions of PARP1 and PARP2 in DNA ligase I-independent DNA replication. Nucleic Acids Res. 2024 Aug 6:gkae672. doi: 10.1093/nar/gkae672. Epub ahead of print. PMID: 39106163. 15: Ikeuchi H, Matsuno Y, Kusumoto-Matsuo R, Kojima S, Ueno T, Ikegami M, Kitada R, Sumiyoshi-Okuma H, Kojima Y, Yonemori K, Yatabe Y, Takamochi K, Suzuki K, Yoshioka KI, Mano H, Kohsaka S. GLI1 confers resistance to PARP inhibitors by activating the DNA damage repair pathway. Oncogene. 2024 Aug 3. doi: 10.1038/s41388-024-03105-1. Epub ahead of print. PMID: 39095584. 16: Kao YH, Falzone N, Pearson M, Pook D, Sivaratnam D. 177Lu-PSMA With Olaparib Radiosensitization Potentiates Response and Toxicity in Extensive Castration- Resistant Metastatic Prostate cancer. Clin Nucl Med. 2024 Aug 2. doi: 10.1097/RLU.0000000000005390. Epub ahead of print. PMID: 39093035. 17: Lv Z, Ali A, Zou C, Wang Z, Ma M, Cheng N, Shad M, Hao H, Zhang Y, Rahman FU. Salicylaldehyde-derived piperazine-functionalized hydrazone ligand-based Pt(II) complexes: inhibition of EZH2-dependent tumorigenesis in pancreatic ductal adenocarcinoma, synergism with PARP inhibitors and enhanced apoptosis. Dalton Trans. 2024 Aug 2. doi: 10.1039/d4dt01243g. Epub ahead of print. PMID: 39091221. 18: Bilen MA, Khilfeh I, Rossi C, Morrison L, Diaz L, Hilts A, Lefebvre P, Pilon D, George DJ. Treatment patterns for patients with BRCA1/2-positive metastatic castration-resistant prostate cancer. Oncologist. 2024 Jul 31:oyae183. doi: 10.1093/oncolo/oyae183. Epub ahead of print. PMID: 39083346. 19: Funo T, Hashimoto D, Yamaki S, Matsumura K, Miyazaki H, Matsui Y, Tsybulskyi D, Sang NT, Yaolin X, Satoi S. Conversion surgery for BRCA-mutated pancreatic ductal adenocarcinoma with liver metastasis treated with platinum-based chemotherapy followed by olaparib. Surg Case Rep. 2024 Jul 30;10(1):179. doi: 10.1186/s40792-024-01975-x. PMID: 39078424; PMCID: PMC11289193. 20: Chen L, Ren Z, Zhang Y, Hou W, Li Y. Design, synthesis, and evaluation of novel stilbene derivatives that degrade acidic nucleoplasmic DNA-binding protein 1 (And1) and synergize with PARP1 inhibitor in NSCLC cells. J Enzyme Inhib Med Chem. 2024 Dec;39(1):2383886. doi: 10.1080/14756366.2024.2383886. Epub 2024 Jul 29. PMID: 39072709; PMCID: PMC11288208.

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