1174043-16-3

1174043-16-3 structure

Name: AZD2461
Chemical Name: 4-[[4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one
CAS Number: 1174043-16-3
Molecular Formula: C₂₂H₂₂FN₃O₃
Molecular Weight: 395.427
Catalog: Biochemical Inhibitor DNA damage PARP inhibitor
Create Date: 2017-05-08 01:46:56
Modify Date: 2024-01-02 23:04:10
AZD-2461 is a potent PARP inhibitor, with IC50s of 5 nM, 2 nM and 200 nM for PARP1, PARP2 and PARP3, respectively.

Name	4-[[4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one
Synonyms	1(2H)-Phthalazinone, 4-[[4-fluoro-3-[(4-methoxy-1-piperidinyl)carbonyl]phenyl]methyl]- 4-[4-Fluoro-3-[(4-methoxypiperidin-1-yl)carbonyl]benzyl]phthalazin-1(2H)-one 1(2H)-Phthalazinone,4-[[4-fluoro-3-[(4-methoxy-1-piperidinyl)carbonyl]phenyl]methyl] AZD2461 CS-1402 4-{4-Fluoro-3-[(4-methoxy-1-piperidinyl)carbonyl]benzyl}-1(2H)-phthalazinone AZD-2461\|\|AZD 2461 S7029,AZD 2461 4-(4-fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one AZD-2461

Description	AZD-2461 is a potent PARP inhibitor, with IC50s of 5 nM, 2 nM and 200 nM for PARP1, PARP2 and PARP3, respectively.
Related Catalog	Research Areas >> Cancer
Target	PARP2:2 nM (IC50) PARP1:5 nM (IC50) PARP3:200 nM (IC50)
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[1]. 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)[2].
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[1]. 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[3].
Cell Assay	BT-20 and SKBr-3 human primary breast cancer cell lines are used in the assay. SKBr-3 cells are cultivated in DMEM medium with 10% FCS and BT-20 in RPMI medium under an atmosphere containing 5% CO2. Twenty four hours after plating (at 60-70% confluence), the cells are treated with the PARP-1 inhibitors NU1025, AZD-2461, iniparib, olaparib, and rucaparib at concentrations ranging from 50 to 200 μM, 5 to 50 μM, 5 to 50 μM, 1 to 10 μM, and 0.3 to 10 μM, respectively, for durations indicated in figures 1-7[2].
Animal Admin	Starting from 2 weeks after transplantation into mice, tumor size is monitored at least 3 times a week. All treatments are started when tumors reach a size of approximately 200 mm3. Olaparib (50 mg/kg intraperitoneally) and AZD-2461 (100 mg/kg per os) are given for 28 consecutive days, unless otherwise indicated. If tumors do not shrink below 50% of the initial volume, treatment is continued for another 28 days; otherwise, a new treatment cycle of 28 days is started when the relapsing tumor reaches a size of 100% of the original volume. AZD-2461 is diluted in 0.5% w/v hydroxypropyl methylcellulose in deionized water to a concentration of 10 mg/mL[3].
References	[1]. Oplustil O'Connor L, et al. The PARP Inhibitor AZD2461 Provides Insights into the Role of PARP3 Inhibition for Both Synthetic Lethality and Tolerability with Chemotherapy in Preclinical Models. Cancer Res. 2016 Oct 15;76(20):6084-6094. Epub 2016 Aug 22. [2]. Węsierska-Gądek J, et al. Differential Potential of Pharmacological PARP Inhibitors for Inhibiting Cell Proliferation and Inducing Apoptosis in Human Breast Cancer Cells. J Cell Biochem. 2015 Dec;116(12):2824-39. [3]. Jaspers JE, et al. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov. 2013 Jan;3(1):68-81.

Density	1.3±0.1 g/cm3
Molecular Formula	C₂₂H₂₂FN₃O₃
Molecular Weight	395.427
Exact Mass	395.164520
PSA	75.55000
LogP	0.53
Index of Refraction	1.640
Storage condition	-20°C

763114-26-7

4045-25-4

~74%

1174043-16-3

Literature: ASTRAZENECA AB Patent: US2011/15393 A1, 2011 ; Location in patent: Page/Page column 7 ;

763114-26-7

4045-24-3

~60%

1174043-16-3

Literature: MENEAR, Keith Allan; Javaid, Muhammad Hashim; Gomez, Sylvie; Hummersone, Marc Geoffrey; Lence, Carlos Fenandez; Martin, Niall Morrison Barr; Rudge, David Alan; Roberts, Craig Anthony; Blades, Kevin Patent: US2009/192156 A1, 2009 ; Location in patent: Page/Page column 66 ;

Precursor 3
763114-26-7 4045-25-4 4045-24-3
DownStream 0

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