Abstract
Design and discovery of new classes of anticancer agents with unique mechanisms of action is an urgent medical need. During the past several years, a series of salicylhydrazide class of compounds were reported to possess remarkable potency in a large panel of cancer cell lines from different tumor origins. In particular, the optimized lead compound, SC144, was further investigated and selected as a valuable drug candidate endowed with favorable pharmacokinetic and antiproliferative properties in various in vitro and in vivo xenograft models. This lead compound is active in cells resistant to conventional chemotherapies, synergistic with several standard-of-care drugs, and possesses an unique mechanism acting through the inhibition of the gp130-STAT3-survivin axis. Because of this novel mechanism, clinical development of SC144 will provide new therapeutic options for diverse cancers.
Keywords: Anticancer agents, cytotoxicity, gp130, hydrazides, IL-24, pyrroloquinoxaline, survivin.
Mini-Reviews in Medicinal Chemistry
Title:Identification and Preclinical Evaluation of SC144, a Novel Pyrroloquinoxaline Derivative with Broad-Spectrum Anticancer Activity
Volume: 16 Issue: 8
Author(s): Fedora Grande, Francesca Aiello, Antonio Garofalo and Nouri Neamati
Affiliation:
Keywords: Anticancer agents, cytotoxicity, gp130, hydrazides, IL-24, pyrroloquinoxaline, survivin.
Abstract: Design and discovery of new classes of anticancer agents with unique mechanisms of action is an urgent medical need. During the past several years, a series of salicylhydrazide class of compounds were reported to possess remarkable potency in a large panel of cancer cell lines from different tumor origins. In particular, the optimized lead compound, SC144, was further investigated and selected as a valuable drug candidate endowed with favorable pharmacokinetic and antiproliferative properties in various in vitro and in vivo xenograft models. This lead compound is active in cells resistant to conventional chemotherapies, synergistic with several standard-of-care drugs, and possesses an unique mechanism acting through the inhibition of the gp130-STAT3-survivin axis. Because of this novel mechanism, clinical development of SC144 will provide new therapeutic options for diverse cancers.
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Grande Fedora, Aiello Francesca, Garofalo Antonio and Neamati Nouri, Identification and Preclinical Evaluation of SC144, a Novel Pyrroloquinoxaline Derivative with Broad-Spectrum Anticancer Activity, Mini-Reviews in Medicinal Chemistry 2016; 16 (8) . https://dx.doi.org/10.2174/138955751608160307175649
DOI https://dx.doi.org/10.2174/138955751608160307175649 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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