AZD-2461, CAS No. 1174043-16-3, is a novel and potent PARP inhibitor with lower affinity to P-glycoprotein. AZD2641 is currently in Phase I clinical study. The study is being conducted to see how it may work to treat solid tumors. The main purpose is to establish a safe dosage of the drug and provide additional information on any potential side effects this drug may cause. The study will also assess the blood levels and action of AZD2461 in the body over a period of time and will indicate whether the drug has a therapeutic effect on solid tumors.

Product information

CAS Number: 1174043-16-3

Molecular Weight: 395.43

Formula: C22H22FN3O3

Synonym:

AZD-2461

AZD 2461

AZD2461

Chemical Name: 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

Smiles: COC1CCN(CC1)C(=O)C1=CC(CC2=NNC(=O)C3=CC=CC=C23)=CC=C1F

InChiKey: HYNBNUYQTQIHJK-UHFFFAOYSA-N

InChi: InChI=1S/C22H22FN3O3/c1-29-15-8-10-26(11-9-15)22(28)18-12-14(6-7-19(18)23)13-20-16-4-2-3-5-17(16)21(27)25-24-20/h2-7,12,15H,8-11,13H2,1H3,(H,25,27)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

AZD-2461 is a potent PARP inhibitor, with IC50s of 5 nM, 2 nM and 200 nM for PARP1, PARP2 and PARP3, respectively. AZD-2461 (500 nM) shows inhibitory activity against DNA single-strand break repair in human A459 cells. AZD-2461 cuases resistance and high P-gp expression levels in BRCA2-deficient mouse breast cancer line KB2P3.4. AZD-2461 is cytotoxic to BT-20 cells (5-50 μM), increases the proportions of S- and G2-phase BT-20 cells (5-20 μM), and weakly affects the progression of cell cycle in SKBr-3 cells (5-20 μM).

In Vivo:

AZD-2461 (10 mg/kg, p.o.) enhances the antitumor activity of temozolomide in a mouse colorectal xenograft and exhibits low effect on mouse bone marrow cells. However, the increased bone marrow tolerability of AZD-2461 is not seen in rat models. AZD-2461 (0.5% v/w HPMC, p.o.) increases the survival of mice bearing KB1P tumors after short-term treatment, and long-term treatment is well tolerated, but can not lead to tumor eradication.

References:

1. Jaspers JE, Kersbergen A, Boon U, Sol W, van Deemter L, Zander SA, Drost R, Wientjens E, Ji J, Aly A, Doroshow JH, Cranston A, Martin NM, Lau A, O'Connor MJ, Ganesan S, Borst P, Jonkers J, Rottenberg S. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov. 2013 Jan;3(1):68-81. doi: 10.1158/2159-8290.CD-12-0049. Epub 2012 Oct 25. PubMed PMID: 23103855.

Products are for research use only. Not for human use.