Olaparib (AZD-2281)
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MedKoo CAT#: 200422

CAS#: 763113-22-0

Description: 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

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Olaparib (AZD-2281)
CAS# 763113-22-0
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 200422
Name: Olaparib (AZD-2281)
CAS#: 763113-22-0
Chemical Formula: C24H23FN4O3
Exact Mass: 434.18
Molecular Weight: 434.460
Elemental Analysis: C, 66.35; H, 5.34; F, 4.37; N, 12.90; O, 11.05

Price and Availability

Size Price Availability Quantity
200mg USD 90 Ready to ship
500mg USD 150 Ready to ship
1g USD 250 Ready to ship
2g USD 450 Ready to ship
5g USD 950 Ready to ship
10g USD 1650 Ready to ship
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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).        

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 10.0 23.00

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.

Recalculate based on batch purity %
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: 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.
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.

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1: Faraoni I, Compagnone M, Lavorgna S, Angelini DF, Cencioni MT, Piras E, Panetta P, Ottone T, Dolci S, Venditti A, Graziani G, Lo-Coco F. BRCA1, PARP1 and γH2AX in acute myeloid leukemia: Role as biomarkers of response to the PARP inhibitor olaparib. Biochim Biophys Acta. 2014 Dec 5. pii: S0925-4439(14)00365-2. doi: 10.1016/j.bbadis.2014.12.001. [Epub ahead of print] PubMed PMID: 25483710.

2: Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Spaček J, Vuylsteke P, Hirte H, Mahner S, Plante M, Schmalfeldt B, Mackay H, Rowbottom J, Lowe ES, Dougherty B, Barrett JC, Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2014 Dec 3. pii: S1470-2045(14)71135-0. doi: 10.1016/S1470-2045(14)71135-0. [Epub ahead of print] PubMed PMID: 25481791.

3: Kapoor K, Singla E, Sahu B, Naura AS. PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice. Mol Cell Biochem. 2014 Nov 18. [Epub ahead of print] PubMed PMID: 25404465.

4: Choy E, Butrynski JE, Harmon DC, Morgan JA, George S, Wagner AJ, D'Adamo D, Cote GM, Flamand Y, Benes CH, Haber DA, Baselga JM, Demetri GD. Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy. BMC Cancer. 2014 Nov 5;14:813. doi: 10.1186/1471-2407-14-813. PubMed PMID: 25374341; PubMed Central PMCID: PMC4230717.

5: Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. J Clin Oncol. 2014 Nov 3. pii: JCO.2014.56.2728. [Epub ahead of print] PubMed PMID: 25366685.

6: Yamauchi T, Uzui K, Nishi R, Shigemi H, Ueda T. Gemtuzumab ozogamicin and olaparib exert synergistic cytotoxicity in CD33-positive HL-60 myeloid leukemia cells. Anticancer Res. 2014 Oct;34(10):5487-94. PubMed PMID: 25275045.

7: Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014 Oct;15(11):1207-14. doi: 10.1016/S1470-2045(14)70391-2. Epub 2014 Sep 10. PubMed PMID: 25218906.

8: Gilabert M, Launay S, Ginestier C, Bertucci F, Audebert S, Pophillat M, Toiron Y, Baudelet E, Finetti P, Noguchi T, Sobol H, Birnbaum D, Borg JP, Charafe-Jauffret E, Gonçalves A. Poly(ADP-ribose) polymerase 1 (PARP1) overexpression in human breast cancer stem cells and resistance to olaparib. PLoS One. 2014 Aug 21;9(8):e104302. doi: 10.1371/journal.pone.0104302. eCollection 2014. PubMed PMID: 25144364; PubMed Central PMCID: PMC4140711.

9: Passaro C, Volpe M, Botta G, Scamardella E, Perruolo G, Gillespie D, Libertini S, Portella G. PARP inhibitor olaparib increases the oncolytic activity of dl922-947 in in vitro and in vivo model of anaplastic thyroid carcinoma. Mol Oncol. 2014 Aug 2. pii: S1574-7891(14)00177-X. doi: 10.1016/j.molonc.2014.07.022. [Epub ahead of print] PubMed PMID: 25139258.

10: Orta ML, Höglund A, Calderón-Montaño JM, Domínguez I, Burgos-Morón E, Visnes T, Pastor N, Ström C, López-lázaro M, Helleday T. The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2'-deoxycytidine lesions. Nucleic Acids Res. 2014;42(14):9108-20. doi: 10.1093/nar/gku638. Epub 2014 Jul 29. PubMed PMID: 25074383.

1. Bannigan P, Bao Z, Hickman RJ, Aldeghi M, Häse F, Aspuru-Guzik A, Allen C. Machine learning models to accelerate the design of polymeric long-acting injectables. Nat Commun. 2023 Jan 10;14(1):35. doi: 10.1038/s41467-022-35343-w. PMID: 36627280; PMCID: PMC9832011.

2. Xiang Y, Laurent B, Hsu CH, Nachtergaele S, Lu Z, Sheng W, Xu C, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y. RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature. 2017 Mar 23;543(7646):573-576. doi: 10.1038/nature21671. Epub 2017 Mar 15. Erratum in: Nature. 2017 Nov 29;: PMID: 28297716; PMCID: PMC5490984.

3. Roux C, Jafari SM, Shinde R, Duncan G, Cescon DW, Silvester J, Chu MF, Hodgson K, Berger T, Wakeham A, Palomero L, Garcia-Valero M, Pujana MA, Mak TW, McGaha TL, Cappello P, Gorrini C. Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1. Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4326-4335. doi: 10.1073/pnas.1819473116. Epub 2019 Feb 15. PMID: 30770442; PMCID: PMC6410837..