Home>>Signaling Pathways>> Ubiquitination/ Proteasome>> Autophagy>>Olaparib (AZD2281, Ku-0059436)

Olaparib (AZD2281, Ku-0059436) (Synonyms: AZD 2281, Ku0059436)

Catalog No.GC17580

A PARP inhibitor

Products are for research use only. Not for human use. We do not sell to patients.

Olaparib (AZD2281, Ku-0059436) Chemical Structure

Cas No.: 763113-22-0

Size Price Stock Qty
10mM (in 1mL DMSO)
$41.00
In stock
10mg
$36.00
In stock
100mg
$112.00
In stock
500mg
$473.00
In stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Customer Reviews

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product has been cited by 2 publications

Product Documents

Quality Control & SDS

View current batch:

Protocol

Kinase experiment [1]:

Preparation Method

Measured PARP-2 activity inhibition by using a variation of the PARP-1 assay in which PARP-2 protein (recombinant) was bound down by a PARP-2 specific antibody in a 96-well white-walled plate. PARP-2 activity was measured following 3H NAD+ DNA additions. After washing, scintillant was added to measure 3H-incorporated ribosylations. For tankyrase-1,HIS-tagged recombinant TANK-1 protein was incubated with biotinylated NAD+. Alpha beads were added to bind the HIS and biotin tags to create a proximity signal, whereas the inhibition of TANK-1 activity was directly proportional to the loss of this signal.

Reaction Conditions

5 different concentrations of Olaparib (AZD2281, Ku-0059436)(in the range around the predetermined IC50 value)

Applications

Olaparib (AZD2281, KU0059436) is a selective PARP1/2 inhibitor with IC50 of 5 nM/1 nM, and its effect on PARP1/2 is 300 times higher than that of Tankyrase-1.

Cell experiment [2]:

Cell lines

Breast cancer MDA-MB-463 and HCC1937 cell

Preparation Method

Cells were seeded in six-well plates and left overnight Vector control (DMSO) or increasing concentrations of Olaparib (AZD2281, Ku-0059436)(up to 4 μM) were added to the cells and, depending on the cell type, the mixture was left for 7-14 days before counting surviving colonies

Reaction Conditions

4 μM Olaparib (AZD2281, Ku-0059436)for 7-14 days

Applications

Brca1-deficient cell lines were highly sensitive to PARP inhibition by Olaparib (AZD2281, Ku-0059436)

Animal experiment [3]:

Animal models

Mice(The SW620 cell tumor model)

Preparation Method

Animals carrying SW620 xenograft tumors were treated with Olaparib (AZD2281, Ku-0059436) (10mg/kg) in combination with TMZ(50mg/kg) once daily for 5 days

Dosage form

10mg/kg Olaparib (AZD2281, Ku-0059436) for 5 days( oral administration)

Applications

Considerable inhibition of tumor volumes as compared with that of the TMZ alone group was observed for the TMZ plus Olaparib (AZD2281, Ku-0059436) combination. This equated to over 80% tumor growth inhibition throughout the entire terminal phase of the study between TMZ treatment and the combination.

References:

[1]. Menear KA, Adcock C,et,al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008 Oct 23;51(20):6581-91. doi: 10.1021/jm8001263. Epub 2008 Sep 19. PMID: 18800822.

Background

Olaparib (AZD2281, Ku-0059436) is a potent and selective PARP inhibitor that specifically targets PARP1 and PARP2 (IC 50 = 5 nM and 1 nM, respectively). [1].It is an activator of autophagy and mitophagy.

Brca1-deficient cell lines were highly sensitive to PARP inhibition by Olaparib (AZD2281, Ku-0059436)[1]. Olaparib (AZD2281, Ku-0059436) enhances radiotherapy, not only by inhibiting DNA repair but also by changing tumor vascular hemodynamics in non-small cell lung carcinoma (NSCLC). In irradiated Calu-6 and A549 cells, Olaparib (AZD2281, Ku-0059436) enhanced the cytotoxic effects of radiation (sensitizer enhancement ratio at 10% survival = 1.5 and 1.3) and DNA double-strand breaks persisted for at least 24 hours after treatment[2]. PTEN-deficient endometrioid endometrial cancer cells are not responsive to PARP inhibitor Olaparib (AZD2281, Ku-0059436) alone, but instead show superior sensitivity to compound inhibition with PI3K inhibitor BKM120, as evidenced by reduced clonogenic cell growth and three-dimensional (3D) spheroid disintegration[4].

Considerable inhibition of tumor volumes as compared with that of the TMZ alone group was observed for the TMZ plus Olaparib (AZD2281, Ku-0059436)combination. This equated to over 80% tumor growth inhibition throughout the entire terminal phase of the study between TMZ treatment and the combination[1]. The PARP inhibitor AZD2281 (olaparib) showed synergetic effects with cisplatin in a dose-dependent manner. Combinatorial treatment with cisplatin and AZD2281 significantly inhibited xenografted tumor growth compared with single treatment of cisplatin or Olaparib (AZD2281, Ku-0059436)[3]. Treatment of tumor-bearing mice with AZD2281 inhibited tumor growth without signs of toxicity, resulting in strongly increased survival. Long-term treatment with Olaparib (AZD2281, Ku-0059436) in this model did result in the development of drug resistance[5]. DNA damage denoted by γH2AX foci was completely undetectable in primordial follicles of control animals but was observed in 10% of surviving primordial follicle oocytes in mice treated with Olaparib (AZD2281, Ku-0059436) alone[7]. When explored the possible combination of the PAPRi Olaparib (AZD2281, Ku-0059436) with EGFRvIII-targeted CAR (806-28Z CAR) T cells in immunocompetent mouse models of breast cancer.The administration of Olaparib (AZD2281, Ku-0059436) could significantly enhance the efficacy of 806-28Z CAR-T cells in vivo. Olaparib (AZD2281, Ku-0059436) could suppress myeloid-derived suppressor cell (MDSC) migration and promote the survival of CD8+ T cells in tumor tissue[6].

References:
[1]: Menear KA, Adcock C,et,al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008 Oct 23;51(20):6581-91. doi: 10.1021/jm8001263. Epub 2008 Sep 19. PMID: 18800822.
[2]: Senra JM, Telfer BA, et,al. Inhibition of PARP-1 by olaparib (AZD2281) increases the radiosensitivity of a lung tumor xenograft. Mol Cancer Ther. 2011 Oct;10(10):1949-58. doi: 10.1158/1535-7163.MCT-11-0278. Epub 2011 Aug 8. PMID: 21825006; PMCID: PMC3192032.
[3]: Yasukawa M, Fujihara H, et,al. Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo. Int J Mol Sci. 2016 Feb 24;17(3):272. doi: 10.3390/ijms17030272. PMID: 26927065; PMCID: PMC4813136.
[4]: Bian X, Gao J, et,al. PTEN deficiency sensitizes endometrioid endometrial cancer to compound PARP-PI3K inhibition but not PARP inhibition as monotherapy. Oncogene. 2018 Jan 18;37(3):341-351. doi: 10.1038/onc.2017.326. Epub 2017 Sep 25. PMID: 28945226; PMCID: PMC5799770.
[5]: Rottenberg S, Jaspers JE, 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 U S A. 2008 Nov 4;105(44):17079-84. doi: 10.1073/pnas.0806092105. Epub 2008 Oct 29. PMID: 18971340; PMCID: PMC2579381.
[6]: Sun R, Luo H, et,al.Olaparib Suppresses MDSC Recruitment via SDF1α/CXCR4 Axis to Improve the Anti-tumor Efficacy of CAR-T Cells on Breast Cancer in Mice. Mol Ther. 2021 Jan 6;29(1):60-74. doi: 10.1016/j.ymthe.2020.09.034. Epub 2020 Sep 26. PMID: 33010818; PMCID: PMC7791086.
[7]: Winship AL, Griffiths M, et,al. The PARP inhibitor, olaparib, depletes the ovarian reserve in mice: implications for fertility preservation. Hum Reprod. 2020 Aug 1;35(8):1864-1874. doi: 10.1093/humrep/deaa128. PMID: 32604417.

Chemical Properties

Cas No. 763113-22-0 SDF
Synonyms AZD 2281, Ku0059436
Chemical Name 4-[[3-[4-(cyclopropanecarbonyl)piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one
Canonical SMILES C1CC1C(=O)N2CCN(CC2)C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
Formula C24H23FN4O3 M.Wt 434.46
Solubility ≥ 21.72 mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.3017 mL 11.5085 mL 23.0171 mL
5 mM 0.4603 mL 2.3017 mL 4.6034 mL
10 mM 0.2302 mL 1.1509 mL 2.3017 mL
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

Review for Olaparib (AZD2281, Ku-0059436)

Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for Olaparib (AZD2281, Ku-0059436)

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.