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Chromatin/Epigenetic PARP Olaparib

Olaparib

Catalog No. T3015   CAS 763113-22-0
Synonyms: KU0059436, AZD2281

Olaparib is a small molecule inhibitor of PARP1/PARP2 (IC50: 5/1 nM) but is less effective against the PARP tankyrase-1 (IC50: 1.5 µM).

Olaparib, CAS 763113-22-0
Pack Size Availability Price/USD Quantity
2 mg In stock 26.00
5 mg In stock 45.00
10 mg In stock 59.00
50 mg In stock 80.00
100 mg In stock 102.00
200 mg In stock 134.00
500 mg In stock 199.00
1 g In stock 275.00
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Biological Description
Chemical Properties
Storage & Solubility Information
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Description Olaparib is a small molecule inhibitor of PARP1/PARP2 (IC50: 5/1 nM) but is less effective against the PARP tankyrase-1 (IC50: 1.5 µM).
Targets&IC50 PARP1 : ic50 5 nM (cell free),   PARP2 : ic50 1 nM (cell free),  
In vivo Animals bearing SW620 xenografted tumors were treated with AZD2281 (10 mg/kg, po) in combination with TMZ (50 mg/kg, po) once daily for 5 consecutive days, after which the tumors were left to grow out. A considerable inhibition of tumor volumes as compared with that of the TMZ alone group was observed for the TMZ plus AZD2281 combinations [1]. Tumor volumes of control group mice increased during the experimental period. The tumor growth of cisplatin and AZD2281 (25 mg/kg/day, every three days for five treatments) groups significantly decreased compared to the control group, and that of combination group was further decreased [2]. Combination treatment of Calu-6 xenografts with olaparib and fractionated radiotherapy caused significant tumor regression relative to radiotherapy alone. Olaparib alone, when given as single or multiple daily doses, or in combination with fractionated radiotherapy, increased the perfusion of tumor blood vessels [4].
Kinase Assay This assay determined the ability of test compounds to inhibit PARP-1 enzyme activity. The method that was used was as reported. We 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 3 H-incorporated ribosylations. For tankyrase-1, an AlphaScreen assay was developed in which HIS-tagged recombinant TANK-1 protein was incubated with biotinylated NAD+ in a 384-well ProxiPlate assay. 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. All experiments were repeated at least three times [1].
Cell Research
HSC-2, Ca9-22, and SAS oral carcinoma cells were seeded in 24-well plates at a density of 2 × 104 cells/well. After overnight incubation, the culture medium was replaced with fresh medium containing various concentrations of PARP inhibitor AZD228 or cisplatin. After 24 h of treatment, the number of viable cells was assessed using an MTT assay as reported previously. Briefly, one-tenth of the fluid volume of 5 mg/mL MTT in RPMI-1640 medium was added to each well, followed by incubation for 4 h at 37 °C. After incubation, the medium was carefully removed and an adequate volume of 0.1 N HCl in isopropanol was added to each well and the resultant formazan crystals was dissolved. Absorbance was determined at 570 nm by microplate reader in 96-well assay plates. All experiments were performed in triplicate [2].
Cell lines: Breast cancer cell lines including SW620 colon, A2780 ovarian, HCC1937, Hs578T, MDA-MB-231, MDA-MB-436, and T47D
Animal Research
Once the tumor diameter had reached 7 mm, the mice were randomly assigned to the following groups: (a) control (200 μL saline); (b) cisplatin (2 mg/kg per body weight, dissolved in 200 μL sterilized water); (c) AZD2281 (25 mg/kg per body weight, dissolved in 200 μL sterilized water); or (d) combination (both cisplatin and AZD2281). The chemicals were administered intraperitoneally every three days, five times. Although AZD2281 is administered orally in the clinic, intraperitoneal injection was recommended by the manufacturer because of easier manipulation and the ethical constraints associated with oral gavage administration to mice. Tumor size and body weight were measured at the time of administration. The tumor volume was calculated using following equation. Tumor volume = verticality × width × height × 0.5236 Three days after the last administration, all surviving mice were sacrificed [2].
Animal Model: Brca1-/-;p53-/- mammary tumors are generated in K14cre;Brca1F/F;p53F/F mice.
Synonyms KU0059436 , AZD2281
Purity 100.00%
Molecular Weight 434.46
Formula C24H23FN4O3
CAS No. 763113-22-0

Storage

0-4℃ for short term (days to weeks), or -20℃ for long term (months).

Solubility Information

DMSO: 80 mg/mL (184.1 mM)

Ethanol: <1 mg/mL

Water: <1 mg/mL

( < 1 mg/ml refers to the product slightly soluble or insoluble )

Solution 1

15% Captisol: 15 mg/mL

Citations

References and Literature
1. Menear KA, 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. 1. Menear KA, et al. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-J Med Chem. 2008 Oct 23;51(20):6581-91. 2. Yasukawa M, et al. Synergetic Effects of PARP Inhibitor AZD2281 in Oral Squamous Cell Carcinoma in Vitro and in Vivo. Int J Mol Sci. 2016 Feb 24;17(3):272. 3. Evers B, et al. Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin. Clin Cancer Res. 2008 Jun 15;14(12):3916-25. 4. Senra JM, 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. 5. Su G, Qin L, Su X, et al. Gender‐dependent pharmacokinetics of olaparib in rats determined by ultra‐high performance liquid chromatography/electrospray ionization tandem mass spectrometry[J]. Biomedical Chromatography. 2020: e4791. 5. Bian X, 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.

Related compound libraries

This product is contained In the following compound libraries:
Approved Drug Library Bioactive Compound Library Inhibitor Library Anti-cancer Compound Library Autophagy Compound Library Epigenetics Compound Library FDA-approved Drug Library DNA Damage & Repair Compound Library Anti-cancer Approved drug Library Fluorochemical Library CNS-Penetrant Compound Library

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