A4154-10mg | Olaparib (AZD2281, Ku-0059436) [763113-22-0] Biotrend

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

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9. Kim DS, Camacho CV, et al. "Activation of PARP-1 by snoRNAs Controls Ribosome Biogenesis and Cell Growth via the RNA Helicase DDX21." Mol Cell. 2019 Jul 9. pii: S1097-2765(19)30476-9. PMID: 31351877
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Storage	Store at -20°C
M.Wt	434.46
Cas No.	763113-22-0
Formula	C₂₄H₂₃FN₄O₃
Synonyms	AZD 2281,AZD-2281
Solubility	≥21.72 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
Chemical Name	4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one
SDF	Download SDF
Canonical SMILES	C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Cell experiment: [1]
Cell lines	Normal LCL cells ATM-null LCL cells
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	10 μM, 1 hour
Applications	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.
Animal experiment: [1]
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.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Weston V J, Oldreive C E, Skowronska A, et al. The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Blood, 2010, 116(22): 4578-4587.

Olaparib (AZD2281, KU0059436) is a potent inhibitor of PARP1 and PARP2 with IC50 of 5 and 1 nM, respectively.
Targets	PARP1	PARP2
IC50	5 nM	1 nM

Purity = 99.80%

Olaparib (AZD2281, Ku-0059436) [763113-22-0]

Katalog-Nummer A4154-10mg

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