2. Academic Validation
  3. 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors

7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors

  • Bioorg Med Chem. 2014 Feb 1;22(3):1089-103. doi: 10.1016/j.bmc.2013.12.031.
Raffaella Cincinelli 1,  Loana Musso 1,  Lucio Merlini 1,  Giuseppe Giannini 2,  Loredana Vesci 2,  Ferdinando M Milazzo 2,  Nives Carenini 3,  Paola Perego 3,  Sergio Penco 2,  Roberto Artali 4,  Franco Zunino 3,  Claudio Pisano 2,  Sabrina Dallavalle 5
Affiliations

Affiliations

  • 1 Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università di Milano, via Celoria 2, 20133 Milano, Italy.
  • 2 R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.,via Pontina Km 30, 400, I-00040 Pomezia (RM), Italy.
  • 3 Molecular Pharmacology Unit, Dept. Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, via Amadeo 42, I-20133 Milan, Italy.
  • 4 Scientia Advice, di Roberto Artali, 20832 Desio (MB), Italy.
  • 5 Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università di Milano, via Celoria 2, 20133 Milano, Italy. Electronic address: sabrina.dallavalle@unimi.it.
PMID: 24398383 DOI: 10.1016/j.bmc.2013.12.031
Abstract

7-Azaindole-1-carboxamides were designed as a new class of PARP-1 inhibitors. The compounds displayed a variable pattern of target inhibition profile that, in part, paralleled the antiproliferative activity in cell lines characterized by homologous recombination defects. A selected compound (1l; ST7710AA1) showed significant in vitro target inhibition and capability to substantially bypass the multidrug resistance mediated by Pgp. In antitumor activity studies against the MX1 human breast carcinoma growth in nude mice, the compound exhibited an effect similar to that of Olaparib in terms of tumor volume inhibition when used at a lower dose than the reference compound. Treatment was well tolerated, as no deaths or significant weight losses were observed among the treated Animals.

Keywords

7-Azaindoles; Antitumor; Molecular modelling; PARP inhibitors; Synthesis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-117423
    PARP-1 抑制剂
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