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| Other names | BMS-217380-01; YMB-1002; DPPE |
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| Formula | C19H25NO |
| Molar mass | 283.415 g·mol−1 |
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Tesmilifene (INN; developmental code namesYMB-1002,BMS-217380-01), also known asN,N-diethyl-2-(4-phenylmethyl)ethanamine (DPPE), is asmall-moleculeantineoplastic drug andchemopotentiator that was under development byYM BioSciences for the treatment ofbreast cancer in the 2000s but was never marketed.[1][2][3] It reachedphase IIIclinical trials foradvanced/metastatic breast cancer before development was discontinued.[1]
Tesmilifene is adiphenylmethanederivative that is structurally related to thetriphenylethylene derivativetamoxifen but lacks thestilbenebridge and thirdphenyl ring necessary for binding to theestrogen receptor (ER), and as such, it is not aselective estrogen receptor modulator (SERM).[4][5] In addition to tamoxifen, tesmilifene is structurally related to diphenylmethaneantihistamines likediphenhydramine andhydroxyzine, but is much weaker than these agents inassays of anti-H1 receptor activity, and hence, neither acts as an antihistamine.[4]
Tamoxifen is known to bind not only to the ER but also to non-ER so-called "antiestrogen binding sites" (AEBS) that are present incellmicrosomes as opposed to thecell nucleus.[4][5] Tesmilifene was developed as a selectiveligand of the AEBS without ERaffinity to investigate these sites and their role in the antineoplastic activity of tamoxifen.[4][5]Histamine has been found to be a ligand of the AEBS, and it has been determined that the AEBS represent thesubstratebinding site of certain microsomalcytochrome P450enzymes includingCYP3A4,CYP2D6, andCYP1A1.[4] Tesmilifene binds to and displaces histamine from these sites equipotently to tamoxifen and more strongly than conventional antihistamines, and this action has been found to correlate with thecytotoxic effects of tesmilifene in breast cancer cellsin vitro.[4] Moreover, in spite of its lack of affinity for the ER, tesmilifeneantagonizes theuterotrophic effects ofexogenousestrogenin vivo.[4]
