SR31747A: a peripheral sigma ligand with potent antitumor activities

SR31747A is currently being evaluated in phase IIb clinical trials for prostate cancer treatment. The molecule is a peripheral sigma ligand that binds four proteins in human cells, i.e. SRBP-1, sigma-2, HSI and its relative SRBP-2. SR31747A is a dual agent with both immunomodulatory and antiprolifer...

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Published inAnti-cancer drugs Vol. 15; no. 2; p. 113
Main Authors Casellas, Pierre, Galiegue, Sylvaine, Bourrie, Bernard, Ferrini, Jean-Bernard, Jbilo, Omar, Vidal, Hubert
Format Journal Article
LanguageEnglish
Published England 01.02.2004
Subjects
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cyclohexanes - pharmacology
Cyclohexanes - therapeutic use
Humans
Immunologic Factors - pharmacology
Immunologic Factors - therapeutic use
Injections, Intraperitoneal
Male
Prostatic Neoplasms - drug therapy
Receptors, sigma - drug effects
Receptors, sigma - metabolism
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Summary:SR31747A is currently being evaluated in phase IIb clinical trials for prostate cancer treatment. The molecule is a peripheral sigma ligand that binds four proteins in human cells, i.e. SRBP-1, sigma-2, HSI and its relative SRBP-2. SR31747A is a dual agent with both immunomodulatory and antiproliferative activities. The molecule blocks proliferation of human and mouse lymphocytes, modulates the expression of pro- and anti-inflammatory cytokines, and was shown to protect animals in vivo against acute and chronic inflammatory conditions such as acute graft-versus-host reaction, lethality induced by staphylococcal enterotoxin B and lipopolysaccharide or rheumatoid arthritis. Besides these immunomodulatory activities, the molecule also inhibits the proliferation of various tumor cell lines in vitro in a time- and concentration-dependent manner. In vivo, SR31747A has potent antitumoral activity as demonstrated against mammary and prostatic tumoral cell lines injected into nude mice, where both tumor incidence and growth were decreased by more than 40% following daily SR31747A treatment at 25 mg/kg i.p. The recent literature on SR31747A in cancer is reviewed here. We focus specifically on preclinical data obtained in vivo and on studies aimed at deciphering the mode of action of the molecule.
ISSN:0959-4973
DOI:10.1097/00001813-200402000-00003