Olaparib (AZD2281)

Catalog No.S1060 Batch:S106022

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Technical Data

Formula

C24H23FN4O3
Molecular Weight 434.46 CAS No. 763113-22-0
Solubility (25°C)* In vitro DMSO 87 mg/mL (200.24 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Olaparib (AZD2281, KU0059436) is a selective inhibitor of PARP1/2 with IC50 of 5 nM/1 nM in cell-free assays, 300-times less effective against tankyrase-1. Olaparib induces significant autophagy that is associated with mitophagy in cells with BRCA mutations.
Targets
PARP2 [1]
(Cell-free assay)		 PARP1 [1]
(Cell-free assay)
1 nM 5 nM
In vitro Olaparib would act against BRCA1 or BRCA2 mutations. Olaparib is not sensitive to tankyrase-1 (IC50 >1 μM). Olaparib could ablate the PARP-1 activity at concentrations of 30-100 nM in SW620 cells. Olaparib is hypersensitive to BRCA1-deficient cell lines (MDA-MB-463 and HCC1937), compared with BRCA1- and BRCA2-proficient cell lines (Hs578T, MDA-MB-231, and T47D). [1] Olaparib is strongly sensitive to KB2P cells due to suppression of base excision repair by PARP inhibition, which may result in the conversion of single-strand breaks to double-strand breaks during DNA replication, thus activating BRCA2-dependent recombination pathways. [2]
In vivo Combining with temozolomide, Olaparib (10 mg/kg, p.o.) significantly suppresses tumor growth in SW620 xenografts. [1] Olaparib shows great response to Brca1-/-;p53-/- mammary tumors (50 mg/kg i.p. per day), while no responses to HR-deficient Ecad-/-;p53-/- mammary tumors. Olaparib even does not show dose-limiting toxicity in tumor-bearing mice. [3] Olaparib has been used to treat with BRCA mutated tumors, such as ovarian, breast and prostate cancers. Moreover, Olaparib shows selectively inhibition to ATM (Ataxia Telangiectasia Mutated)-deficient tumor cells, which indicates to be a potential agent for treating ATM mutant lymphoid tumors. [4]
Features A potent PARP inhibitor (currently in late stage clinical trials).

Protocol (from reference)

Kinase Assay:

[1]
  • FlashPlate assay (96-well screening assay)

    To columns 1 through 10, 1 μL of Olaparib (in DMSO) is added, and 1 μL DMSO only is added to the positive (POS) and negative (NEG) control wells (columns 11 and 12, respectively) of a pretreated FlashPlate. PARP-1 is diluted 1:40 in buffer (buffer B: 10% glycerol (v/v), 25 mM HEPES, 12.5 mM MgCl2,50 mM KCl, 1 mM DTT, 0.01% NP-40 (v/v), pH 7.6) and 40 μL added to all 96 wells (final PARP-1 concentration in the assay is ~1 ng/μL). The plate is sealed and shaken at RT for 15 min. Following this, 10 μL of positive reaction mix (0.2 ng/μL of double-stranded oligonucleotide [M3/M4] DNA per well, 5 μM of NAD+ final assay concentration, and 0.075 μCi 3H-NAD+ per well) is added to the appropriate wells (columns 1-11). The negative reaction mix, lacking the DNA oligonucleotide, is added to column 12 (with the mean negative control value used as the background). The plate is resealed and shaken for a further 60 min at RT to allow the reaction to continue. Then, 50 μL of ice-cold acetic acid (30%) is added to each well to stop the reaction, and the plate is sealed and shaken for a further 60 min at RT. Tritiated signal bound to the FlashPlate is then determined in counts per minute (CPM) using the TopCount plate reader.
Cell Assay:

[1]
  • Cell lines

    Breast cancer cell lines including SW620 colon, A2780 ovarian, HCC1937, Hs578T, MDA-MB-231, MDA-MB-436, and T47D

  • Concentrations

    1-300 nM

  • Incubation Time

    7-14 days

  • Method

    The cytotoxicity of Olaparib is measured by clonogenic assay. Olaparib is dissolved in DMSO and diluted by culture media before use. The cells are seeded in six well plates and left to attach overnight. Then Olaparib is added at various concentrations and the cells are incubated for 7-14 days. After that the surviving colonies are counted for calculating the IC50.
Animal Study:

[3]
  • Animal Models

    Brca1-/-;p53-/- mammary tumors are generated in K14cre;Brca1F/F;p53F/F mice.

  • Dosages

    50 mg/kg

  • Administration

    Administered via i.p. injection at 10 μL/g of body weight

Customer Product Validation

Data from [Data independently produced by Cancer Res, 2014, 74(21), 5948-54]

Data from [Data independently produced by Medicine (Baltimore), 2014, 93(28), e294]

Data from [J Exp Clin Cancer Res, 2013, 32(1), 95]

Data from [Hepatology, 2012, 55, 1840-1851]

Selleck's Olaparib (AZD2281) has been cited by 1216 publications

Transcription-replication conflicts underlie sensitivity to PARP inhibitors [ Nature, 2024, 10.1038/s41586-024-07217-2] PubMed: 38509368
PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends [ Cell, 2024, 187(4):945-961.e18] PubMed: 38320550
FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress [ Nat Commun, 2024, 15(1):866] PubMed: 38286805
Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer [ Cell Rep Med, 2024, 5(2):101396] PubMed: 38290515
DNA damage remodels the MITF interactome to increase melanoma genomic instability [ Genes Dev, 2024, 38(1-2):70-94] PubMed: 38316520
Poly(ADP-ribosyl)ation of TIMELESS limits DNA replication stress and promotes stalled fork protection [ Cell Rep, 2024, 43(3):113845] PubMed: 38393943
The ARID1A-METTL3-m6A axis ensures effective RNase H1-mediated resolution of R-loops and genome stability [ Cell Rep, 2024, 43(2):113779] PubMed: 38358891
CASK Mediates Oxidative Stress-Induced Microglial Apoptosis-Inducing Factor-Independent Parthanatos Cell Death via Promoting PARP-1 Hyperactivation and Mitochondrial Dysfunction [ Antioxidants (Basel), 2024, 13(3)343] PubMed: 38539876
PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics, Senescence, and Oncogenic Transformation [ Cells, 2024, 13(2)159] PubMed: 38247850
Type III secretion system effector YfiD inhibits the activation of host poly(ADP-ribose) polymerase-1 to promote bacterial infection [ Commun Biol, 2024, 7(1):162] PubMed: 38332126

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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