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PARP&Proteasome

A-966492 (934162-61-5)

A-966492 is a novel and potent inhibitor of PARP1 and PARP2 with Ki of 1 nM and 1.5 nM, respectively.

Not Intended for Therapeutic Use. For research use only.

CAS: 934162-61-5 Category

A-966492 (934162-61-5) Description:

A-966492 is one of the most potent PARP inhibitors. A-966492 displays excellent potency against the PARP-1 enzyme with a Kiof 1 nM and an EC50 of 1 nM in a whole cell assay. A-966492 significantly enhances the efficacy of TMZ in a dose-dependent manner. In addition, A-966492 is orally bioavailable across multiple species, crosses the blood−brain barrier, and appears to distribute into tumor tissue. A-966492 represents a promising, structurally diverse benzimidazole analogue and is being further characterized preclinically.

A-966492 also demonstrates good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin. In addition, A-966492 has excellent pharmaceutical properties and has demonstrated in vivo efficacy in preclinical mouse tumor models in combination with TMZ and carboplatin, as well as single agent activity in a BRCA1-deficient MX-1 tumor model. A-966492 is further characterized in Sprague−Dawley rats, beagle dogs, and cynomolgus monkeys, with A-966492 demonstrating oral bioavailabilities of 34−72% and half-lives of 1.7−1.9 hours. In vivo, A-966492 demonstrates significant enhancement of the efficacy of TMZ in a murine B16F10 syngeneic melanoma model, with the A-966492 combination groups showing superior efficacy.

A-966492 (934162-61-5) Specifications:

Product Name A-966492
Synonyms 2-[2-Fluoro-4-[(2S)-2-pyrrolidinyl]phenyl]-1H-benzimidazole-7-carboxamide; A966492; A 966492;
Chemical Name S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide;A-966492(A 966492);2-{2-fluoro-4-[(2S)-pyrrolidin

-2-yl]phenyl}-1H-1,3-benzodiazole-7-carboxaMide;2-[2-Fluoro-4-[(2S)-2-pyrrolidinyl]phenyl]-1H-benzimidazole-7-carboxamide A-966492;

Purity ≥98%
CAS Number 934162-61-5
Molecular Formula C18H17FN4O
Molecular Weight 324.359 g/mol
Monoisotopic Mass 324.139 g/mol
MDL number N/A
InChIKey AHIVQGOUBLVTCB-AWEZNQCLSA-N
InChi Code InChI=1S/C18H17FN4O/c19-13-9-10(14-5-2-8-21-14)6-7-11(13)18-22-15-4-1-3-12(17(20)24)16(15)23-18/h1,3-4,6-7,9,14,21H,2,5,8H2,(H2,20,24)(H,22,23)/t14-/m0/s1
SMILES O=C(C1=C2N=C(C3=CC=C([[email protected]]4NCCC4)C=C3F)NC2=CC=C1)N
Form Powder
Color White
Solubility  Soluble in DMSO, not in water
Storage Temp.  Dry, dark and at 0 – 4 C for short term (days to weeks) or -20 C for long term (months to years).
Shelf life ≥ 2 years
Handling Protect from air and light
Application a potent PARP inhibitor

 


RIDADR NONH for all modes of transport

References:

  • Koosha F, Neshasteh-Riz A, Takavar A, Eyvazzadeh N, Mazaheri Z, Eynali S, Mousavi M. The combination of A-966492 and Topotecan for effective radiosensitization on glioblastoma spheroids. Biochem Biophys Res Commun. 2017 Sep 30;491(4):1092-1097. doi: 10.1016/j.bbrc.2017.08.018. Epub 2017 Aug 7. PMID: 28797568.
  • Penning TD, Zhu GD, Gong J, Thomas S, Gandhi VB, Liu X, Shi Y, Klinghofer V, Johnson EF, Park CH, Fry EH, Donawho CK, Frost DJ, Buchanan FG, Bukofzer GT, Rodriguez LE, Bontcheva-Diaz V, Bouska JJ, Osterling DJ, Olson AM, Marsh KC, Luo Y, Giranda VL. Optimization of phenyl-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious inhibitor. J Med Chem. 2010 Apr 22;53(8):3142-53. doi: 10.1021/jm901775y. PubMed PMID: 20337371