Table 1.

Current Status of New SERMs

Drug Name	Category (Structure)	Effects	Preclinical Results	Clinical Status
Ospemifene*	Tamoxifen-like	Vaginal atrophy treatment	Estrogenic effects on vaginal epithelium that is not observed with tamoxifen or raloxifene [130, 131, 134]	Phase III trial (826 women) relieves vaginal dryness
		Osteoporosis treatment	Inhibits tumor growth in animal models as effective as tamoxifen [137, 138]	Phase II trial (118 women): Comparable to or slightly better than raloxifene [135]
		Breast cancer prevention		Phase III trial planned (detail not available) Not available
				Not available
Arzoxifene* (LY353381)	Raloxifene-like	Breast cancer treatment	Antiestrogenic in breast and endometrium, estrogenic in bone and lipids [172]	Phase III trial (200 patients) inferior to tamoxifen [217]
		Breast cancer prevention	Effective to prevent ER-positive and ER-negative mammary tumors especially in combination with LG100268 [138, 216]	Phase I trials (50 and 76 women) low toxicity and favorable biomarker profile [218]
Lasofoxifene* (CP-336156, Fablyn)	Raloxifene-like	Osteoporosis treatment and prevention	Higher potency than tamoxifen and raloxifene [139]; higher oral bioavailability than raloxifene [54]	Phase III trial (1,907 women) significantly increases bone mineral density compared to placebo, no endometrial effects, no association with thromboembolic disorder [142]
		Vaginal atrophy treatment	Effects similar to tamoxifen to prevent and treat NMUinduced mammary tumor in rats [219]	Phase III trial to compare with raloxifene (CORAL trial, details not available)
		Breast cancer treatment and prevention		Phase III trail (445 patients) improves vaginal atrophy compared to placebo
		Heart disease prevention		Phase III trial (PEARL trial with 8,556 women), reduces ER-positive breast cancer incidence compared to placebo; slightly decreases major coronary disease risk; reduces vertebral and non-vertebral fractures; increases risks of venous thromboembolic events but not stroke; no endometrial effects [SABCS 2008, abstract 11]
Bazedoxifene* (TSE-424 WAY- 140424)	Raloxifene-like	Osteoporosis treatment and prevention	Increases bone density with little uterine or vasomotor effects	Phase III trial (7,492 women) reduces vertebral and nonvertebral fracture incidences, while raloxifene is not effective against non-vertebral fracture [160]
		Breast cancer prevention	Inhibits estrogen-stimulated breast cancer cells growth [154]	Phase III trial (497 women) reduces endometrial thickness, unique property among known SERMs [220]
				Not available

^*Ospemifene- not approved by the FDA

^*Arzoxifene- not approved by the FDA, trials terminated by Eli Lilly

^*Lasofoxifene- not approved by the FDA, approved in the EU

^*Bazedoxifene- not approved by the FDA, approved in the EU.