| Literature DB >> 27238082 |
Michaël Cerezo1, Abdelali Lehraiki1, Antoine Millet2, Florian Rouaud1, Magali Plaisant1, Emilie Jaune1, Thomas Botton1, Cyril Ronco2, Patricia Abbe1, Hella Amdouni2, Thierry Passeron3, Veronique Hofman4, Baharia Mograbi5, Anne-Sophie Dabert-Gay6, Delphine Debayle6, Damien Alcor1, Nabil Rabhi7, Jean-Sébastien Annicotte7, Laurent Héliot8, Mariano Gonzalez-Pisfil8, Caroline Robert9, Solange Moréra10, Armelle Vigouroux10, Philippe Gual11, Maruf M U Ali12, Corine Bertolotto3, Paul Hofman4, Robert Ballotti3, Rachid Benhida13, Stéphane Rocchi14.
Abstract
We have discovered and developed a series of molecules (thiazole benzenesulfonamides). HA15, the lead compound of this series, displayed anti-cancerous activity on all melanoma cells tested, including cells isolated from patients and cells that developed resistance to BRAF inhibitors. Our molecule displayed activity against other liquid and solid tumors. HA15 also exhibited strong efficacy in xenograft mouse models with melanoma cells either sensitive or resistant to BRAF inhibitors. Transcriptomic, proteomic, and biochemical studies identified the chaperone BiP/GRP78/HSPA5 as the specific target of HA15 and demonstrated that the interaction increases ER stress, leading to melanoma cell death by concomitant induction of autophagic and apoptotic mechanisms.Entities:
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Year: 2016 PMID： 27238082 DOI： 10.1016/j.ccell.2016.04.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743