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| Other names | LY-353381 |
| Routes of administration | By mouth |
| Drug class | Selective estrogen receptor modulator |
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| Formula | C28H29NO4S |
| Molar mass | 475.60 g·mol−1 |
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Arzoxifene (INNTooltip International Nonproprietary Name; developmental code nameLY-353381) is aselective estrogen receptor modulator (SERM) of thebenzothiophene group which was never marketed.[1] It is a potentestrogenantagonist in mammary and uterine tissue while acting as an estrogenagonist to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by thecarcinogennitrosomethylurea and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma.
Arzoxifene is aselective estrogen receptor modulator (SERM), and hence is a mixedagonist andantagonist of theestrogen receptor withtissue-selectiveestrogenic andantiestrogenic activity.[2] It has antiestrogenic effects in thebreast, mixed estrogenic and antiestrogenic effects in theuterus, and estrogenic effects inbone.[2] The medication has been found to suppressgonadotropin levels inpostmenopausal women, increasesex hormone-binding globulin levels, and decreaseinsulin-like growth factor 1 andinsulin-like growth factor-binding protein 3 levels.[2]
In a phase 3 clinical study in postmenopausal women, arzoxifene was shown to increase bone spine and hip mineral density and had no effect on the uterus and endometrium.[3]
Lilly announced in August 2009 that preliminary results from a five-year clinical study showed that arzoxifene met its primary endpoints of reduction in vertebral fractures and breast cancer in postmenopausal women. However arzoxifene failed to meet secondary endpoints of reduction in non-vertebral fractures and cardiovascular events and improvements in cognitive function. Based on these results, Lilly announced they are discontinuing further development of the drug and would not seek regulatory approval.[4]
A 2015network meta-analysis found that arzoxifene significantly reduced the risk ofbreast cancer (RRTooltip relative risk = 0.415) and to a greater extent thanraloxifene (RR = 0.572) ortamoxifen (RR = 0.708).[5]
