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763113-22-0 (Olaparib)

1

Identification

Olaparib Olaparib
Name Olaparib
Formula C24H23FN4O3
MW 434.46
CAS No. 763113-22-0
EINECS
Smiles O=C(C1=CC(CC(C2=C3C=CC=C2)=NNC3=O)=CC=C1F)N4CCN(C(C5CC5)=O)CC4
Synonyms AZD2281;KU-0059436;KU0059436;AZD-2281;KU0059436;AZD 2281; 4-(3-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one
InChI 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)
2

Introduction

Olaparib (AZD2281, KU0059436) is a potent PARP inhibitor with IC50 of 5 and 1 nM for PARP-1and PARP-2, respectively. IC50 Value: 5 nM(PARP-1); 1 nM(PARP-2) Target: PARP in vitro: Olaparib would act against BRCA1 or BRCA2 mutations.

Background Information

A highly potent selective and orally bioavailable inhibitor of PARP ......by AOBIOUS INC

Olaparib (4-(3-4-fluorophenyl) methyl-1(2H)-one), as known as AZD2281 or KU0059436, is a novel, selective and potent inhibitor of both poly adenosine diphosphate-ribose polymeras-1 (PARP-1) and poly adenosine diphosphate-ribose polymeras-2 (PARP-2).  Having been successfully used in the treatment of tumors harboring BRCA mutations, olaparib strongly inhibits the growth of BRCA2-deficient mouse mannary tumor cell lines demonstrating cytotoxicity. In previous researches treating non-small cell lung carcinoma (NSCLC), olaparib increased the radiation sensitivity of NSCLC cells, grown as xenografts in nude mice, following radiation and increased vascular perfusion in Calu-6 tumors established in a dorsal window chamber (DWC) model.

Reference

Joana M. Senra, Brian A. Telfer, Kim E. Cherry, Cian M. McCrudden, David G. Hirst, Mark J. O’Connor, Stephen R. Wedge, and Ian J. Stratford. Inhibition of poly(ADP-ribose) polymerase-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft. Mol Cancer Ther. 2011; 10(10): 1949-1958

Bastiaan Evers, Rinske Drost, Eva Schut, Michiel Bruin, Eline vab der Burg, Patrick W.B. Derksen, Henne Holstege, Xiaoling Liu, Ellen van Drunen, H. Berna Beverloo, Graeme C. M. Smith, Niall M. B. Martin, Alan Lau, Mark J. O’Connor, and Jos Jonkers. Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and Cisplatin. Clin Cancer Res 2008; 14:3916-3925

......by Apexbio Technology LLC
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 inhibi ......by BOC Sciences
More than 200 labs worldwide have purchased Olaparib from LC Labs (either directly from us or from our many distributors, many of whom resell under their own labels). Olaparib is a poly(ADP-ribose) polymerase 1 (PARP1) inhibitor and an anti-cancer drug being tested in patients with mutations in the genes BRCA1 or BRCA2. PARP1 acts as a critical molecule in the repair of DNA single-strand breaks (SSBs) and plays an important role in maintaining DNA integrity. de Murcia, J., et al. "Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells." Proc. Natl. Acad. Sci. USA 94: 7303-7307 (1997). PARP inhibitors inhibit PARP1 during S-phase and induce inactivation of SSB repair and thus cause DNA double-strand breaks, which induces BRCA-deficient cancer cell apoptosis. Bryant, H.E., et al. "Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase." Nature 434: 913-917 (2005). Farmer, H., et al. "Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy." Nature 434: 917-921 (2005). The PARP inhibitor olaparib was tested in a genetically engineered mouse model for BRCA1-associated breast cancer. Olaparib inhibited tumor growth and significantly improved survival without signs of toxicity. Rottenberg, S., et al. "High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs." Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008). Long-term treatment with olaparib caused the development of drug resistance, which was induced by up-regulation of Abcb1a/b genes encoding P-glycoprotein efflux pumps. The resistance to olaparib could be overcome by tariquidar, a P-glycoprotein inhibitor. Rottenberg, S., et al. "High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs." Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008). Combination treatment using olaparib with cisplatin or carboplatin improved the recurrence-free and overall survival in a murine model, indicating that olaparib enhances the effect of these DNA-damaging agents. Rottenberg, S., et al. "High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs." Proc. Natl. Acad. Sci. USA 105: 17079-17084 (2008). Olaparib inhibited the growth of BRCA2-deficient versus BRCA2-proficient mammary tumor cells. Combination treatment of olaparib and cisplatin had a synergistic cytotoxicity against BRCA2-deficient cells but not against BRCA2-proficient control cells. Evers, B., et al. "Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin." Clin. Cancer Res. 14: 3916-3925 (2008). Other CAS numbers previously assigned to olaparib, namely 894104-70-2, 937799-91-2, and 1021843-02-6, have been deleted by CAS and are no longer in use. ......by LC Laboratoies
Olaparib is a potent PARP inhibitor with IC50 of 5 and 1 nM for PARP-1 and PARP-2, respectively. ......by MedChemexpress Co., Ltd.
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. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). Shelf life: >2 years if stored properly Drug formulation: This drug may be formulated in DMSO ......by MedKoo Biosciences, Inc.
Olaparib (AZD2281, Ku-0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM, 300-times less effective against tankyrase-1. Phase 1/2. ......by Selleck Chemicals LLC
Olaparib (AZD2281, KU0059436) is a potent PARP inhibitor with IC50 of 5 and 1 nM for PARP-1and PARP-2, respectively. ......by Target Molecule Corp.
3

Protocol(Only for Reference)

Cell Experiment

Cell lines Normal LCL cells ATM-null LCL cells
Conditions 10 μM, 1 hour
Method The sensitivity of cells to olaparib is mediated by absence of Ataxia Telangiectasia Mutated (ATM) activity. Immunoblot analysis revealed that in ATM wild-type LCLs, but not ATM null LCLs, phosphorylation of the ATM-dependent targets ATM S1981 and SMC1 S966 was induced in a dose-dependent manner by olaparib.
Source Apexbio Technology LLC

Animal Experiment

Animal Models Granta-519–engrafted NOD/SCID mice
Dosage Form Intraperitoneal injection, 50 mg/kg/d, for 14 days
Applications Analysis of the percentage of human CD45 staining by FACS analysis revealed a significant reduction in the percentage of Granta-519 cells in the bone marrow and a trend toward reduced tumor cell load in the spleen of mice treated with olaparib compared with those receiving vehicle alone.
Source Apexbio Technology LLC
4

Physical and Chemical Properties

Appearance:White to off-white Solid EBNumber:EB000029091

Storage condition

Store at -20°C by Apexbio Technology LLC
Store at or below -20 oC. by LC Laboratoies
Storage condition:Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). Stock solution storage:0 - 4 C for short term (days to weeks), or -20 C for long term (months). 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. by MedKoo Biosciences, Inc.

Solubility

Soluble in DMSO > 10 mM by Apexbio Technology LLC
Soluble in DMSO at 33 mg/mL; soluble in ethanol at 1.7 mg/mL with slight warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-20 μM buffers, serum, or other additives may increase or decrease the aqueous solubility. by LC Laboratoies
DMSO ≥85mg/mL Water <1.2mg/mL Ethanol ≥5.5mg/mL by MedChemexpress Co., Ltd.
Soluble in DMSO, not in water by MedKoo Biosciences, Inc.
DMSO 87 mg/mL (200 mM) ; Water 0.002 mg/mL (<1 mM) ; Ethanol <1 mg/mL (<1 mM) by Selleck Chemicals LLC
5

Mechanism and Indication

6

Clinical Information

Product Name Sponsor & Collaborators Indications Start Date End Date Phase
Olaparib AstraZeneca plc Metastatic stomach cancer 2013/9/30 2017/12/31 Phase 3 Clinical
Olaparib AstraZeneca plc Ovary tumor 2013/9/30 2020/6/30 Phase 3 Clinical
Olaparib AstraZeneca plc Metastatic ovary cancer 2013/8/31 2022/1/31 Phase 3 Clinical
Olaparib AstraZeneca plc Hormone refractory prostate cancer 2014/1/31 2018/7/31 Phase 2 Clinical
Olaparib Velindre NHS Trust Metastatic non small cell lung cancer 2013/5/31 Phase 2 Clinical
Olaparib - Pre-registration
Olaparib - Launched
7

Safety Data of Olaparib

8

Spectral Information

9

Suppliers List

Company Price and Availability Country/Region
AOBIOUS INC 1mg/USD9() USA
Apexbio Technology LLC USA
BOC Sciences
Biochempartner Co., Ltd China
CHEMSCENE, LLC 10mg/USD60();50mg/USD84() USA
LC Laboratoies 10mg/USD38(In stock);25mg/USD49(In stock);50mg/USD64(In stock);100mg/USD99(In stock);200mg/USD157(In stock);250mg/USD178(In stock);500mg/USD261(In stock);1g/USD455(In stock);2g/USD736(In stock);5g/USD1490(In stock) USA
MedChemexpress Co., Ltd. 10mg/USD60();50mg/USD84() USA
MedKoo Biosciences, Inc. USA
Pure Chemistry Scientific Inc. 100mg/USD26(In stock) USA
Selleck Chemicals LLC 10mg/USD70(In stock);10mM/1mLIn DMSO/USD91(In stock);25mg/USD150(In stock);100mg/USD370(In stock);500mg/USD1270(In stock) USA
Shanghai Haoyuan Chemexpress Co., Ltd. 10mg/USD60();50mg/USD84() China
Shanghai XingMo Biotechnology Co., Ltd. 1g/USD1050(In stock) CHINA
Target Molecule Corp. 2mg/USD25();5mg/USD41();10mg/USD78();25mg/USD142();50mg/USD235() USA
10

Related Products

Other Forms of 763113-22-0

Name CAS No Formula MW
(E)-Crotylbarbital 28360-89-6 C10H14N2O3 210.23
KDR-in-4 408502-06-7 C23H25N3O3 391.4629
YM17E 124900-72-7 C40H56N6O2 652.91
Sigma-LIGAND-1 139652-01-0 C27H33NO4 435.55522
Recilisib 334969-03-8 C16H13ClO4S 336.79
Bemarinone 92210-43-0 C11H12N2O3 220.22
KW-4099 (sodium) 124907-31-9 C29H30NNaO3S 495.61
5-HT6/7 antagonist 1 131999-28-5 C22H20FN3O3 393.41
Teludipine hydrochloride 108700-03-4 C28H39ClN2O6 535.07
MRZ 2-514 202808-11-5 C11H6BrN3O3 308.09

Recommended Compounds in PARP Autophagy

Name CAS No Formula MW
MK-4827 (R-enantiomer) 1038915-58-0 C19H20N4O 320.39
MK-4827 (Racemate) 1038915-75-1 C19H20N4O 320.39
MK-4827 (tosylate) 1038915-73-9 C26H28N4O4S 492.59
Nicotinamide 98-92-0 C6H6N2O 122.12
NVP-TNKS656 1419949-20-4 C27H34N4O5 494.58
JW 55 664993-53-7 C25H26N2O5 434.48
PJ34 344458-19-1 C17H17N3O2 295.34
PJ34 (hydrochloride) 344458-15-7 C17H18ClN3O2 331.8
AZD-2461 1174043-16-3 C22H22FN3O3 395.43
BMN-673 (8R,9S) 1207456-00-5 C19H14F2N6O 380.35
BMN-673 1207456-01-6 C19H14F2N6O 380.35
UPF 1069 1048371-03-4 C17H13NO3 279.29
MK-4827 (hydrochloride) 1038915-64-8 C19H21ClN4O 356.85
MK-4827 1038915-60-4 C19H20N4O 320.39
Rucaparib 283173-50-2 C19H18FN3O 323.36
Rucaparib (phosphate) 459868-92-9 C19H21FN3O5P 421.36
A-966492 934162-61-5 C18H17FN4O 324.35
XAV-939 284028-89-3 C14H11F3N2OS 312.31
AG14361 328543-09-5 C19H20N4O 320.39
INO-1001 3544-24-9 C7H8N2O 136.15

Recommended Compounds in Same Indication

Name CAS No Formula MW
LDK378 1032900-25-6 C28H36ClN5O3S 558.14
Pemetrexed (disodium) 150399-23-8 C20H19N5Na2O6 471.37
TAK-700 (R-form) 752243-39-3 C18H17N3O2 307.35
Volasertib 755038-65-4 C34H50N8O3 618.81
ALK inhibitor 1 761436-81-1 C23H28BrN7O3S 562.48
Afatinib (dimaleate) 850140-73-7 C32H33ClFN5O11 718.08
MGCD-265 analog 875337-44-3 C26H20FN5O2S2 517.5977
KX2-391 897016-82-9 C26H29N3O3 431.53
AT-101 90141-22-3 C30H30O8 518.55
Bicalutamide 90357-06-5 C18H14F4N2O4S 430.37
Tivantinib 905854-02-6 C23H19N3O2 369.42
IDO5L 914471-09-3 C9H7ClFN5O2 271.6356
Enzalutamide 915087-33-1 C21H16F4N4O2S 464.44
Tivozanib 475108-18-0 C22H19ClN4O5 454.86
Sunitinib 557795-19-4 C22H27FN4O2 398.47
Linsitinib 867160-71-2 C26H23N5O 421.49
BIBF 1120 656247-17-5 C31H33N5O4 539.62
Fenretinide 65646-68-6 C26H33NO2 391.55
Retaspimycin 857402-23-4 C31H45N3O8 587.7
Retaspimycin (Hydrochloride) 857402-63-2 C31H46ClN3O8 624.17
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Route of Synthesis

12

References

13

More Information

Olaparib

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