| Identification | Back Directory | [Name]
2-Propenoic acid, 3-[1-[(2,4-dichlorophenyl)methyl]-6-(trifluoromethyl)-1H-indazol-3-yl]- | [CAS]
877773-32-5 | [Synonyms]
Gamendazole
2-Propenoic acid, 3-[1-[(2,4-dichlorophenyl)methyl]-6-(trifluoromethyl)-1H-indazol-3-yl]- | [Molecular Formula]
C18H11Cl2F3N2O2 | [MOL File]
877773-32-5.mol | [Molecular Weight]
415.19 |
| Hazard Information | Back Directory | [Description]
Gamendazole is a novel drug candidate for male contraception. It is an indazole carboxylic acid derived from lonidamine (LND). It has been shown to reduce fertility in male rats without affecting testosterone levels, but human clinical trials have not been started. | [Uses]
Gamendazole, an indazole carboxylic acid (ICA), is an orally active, selective HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A) inhibitor. Gamendazole binds to the C-terminal nucleotide binding pocket of HSP90 and cause downregulation of clients AKT1 and ERBB2, but stabilizes the HSP90 heterocomplex. Gamendazole specifically inhibits the actin bundling function of EEF1A1, but does not bind to the nucleotide docking pocket nor inhibits the ribosome charging or protein translation functions of EEF1A1. Gamendazole, an antispermatogenic compound with antifertility effects, has the potential for reversible non-hormonal male contraceptive agent research[1][2]. | [Definition]
ChEBI: Gamendazole is a member of the class of indazoles that is 3-(indazol-3-yl}prop-2-enoic acid carrying additional 2,4-dichlorobenzyl and trifluoromethyl substituents at positions 1 and 6 respectively. An orally active antispermatogenic compound with antifertility effects that is a potential male contraceptive drug. It has a role as a Hsp90 inhibitor, a eukaryotic translation elongation factor 1alpha 1 inhibitor, a synthetic oral contraceptive and an antispermatogenic agent. It is a member of indazoles, an alpha,beta-unsaturated monocarboxylic acid, an olefinic compound, a dichlorobenzene and an organofluorine compound. It is functionally related to a lonidamine. | [IC 50]
HSP90AB1; EEF1A1; Akt1; ErbB2 | [References]
[1] Joseph S Tash, et al. Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A), and stimulates Il1a transcription in rat Sertoli cells. Biol Reprod. 2008 Jun;78(6):1139-52. DOI:10.1095/biolreprod.107.062679
[2] Joseph S. Tash. Gamendazole: A Potent Antispermatogenic Contraceptive Agent with Novel Targets Hsp90β and eEF1A. Biology of ReproductionIF, Volume 78, Issue Suppl_1, 1 May 2008, Page 91. |
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