Lasofoxifene

Lasofoxifene

Clinical data
Trade names	Fablyn
Routes of administration	Oral
ATC code	G03XC03 (WHO)
Identifiers
IUPAC name (5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol
CAS Number	180916-16-9 N
PubChem CID	216416
IUPHAR/BPS	7542
ChemSpider	187585 Y
UNII	337G83N988
ChEMBL	CHEMBL328190 Y
Chemical and physical data
Formula	C28H31NO2
Molar mass	413.55 g/mol 563.64 g/mol (tartrate)
3D model (Jmol)	Interactive image
SMILES O(c1ccc(cc1)[C@@H]4c2ccc(O)cc2CC[C@@H]4c3ccccc3)CCN5CCCC5
InChI InChI=1S/C28H31NO2/c30-24-11-15-27-23(20-24)10-14-26(21-6-2-1-3-7-21)28(27)22-8-12-25(13-9-22)31-19-18-29-16-4-5-17-29/h1-3,6-9,11-13,15,20,26,28,30H,4-5,10,14,16-19H2/t26-,28+/m1/s1 Y Key:GXESHMAMLJKROZ-IAPPQJPRSA-N Y
NY (what is this?)

Lasofoxifene (INN) (brand name Fablyn) is a non-steroidal selective estrogen receptor modulator (SERM) which is marketed by Pfizer for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy, and the result of an exclusive research collaboration with Ligand Pharmaceuticals (LGND). It also appears to have had a statistically significant effect of reducing breast cancer in women according to a study published in The Journal of the National Cancer Institute.

In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events.

In studies of breast cancer prevention, lasofoxifene showed a 79% reduction in breast cancer incidence and an 83% reduction specific incidence of estrogen receptor-positive breast cancers, which is significantly higher than reductions found with the related SERMs tamoxifen and raloxifene. In accordance, a meta-analysis of SERMs for breast cancer prevention found the highest reduction in risk with lasofoxifene of all the drugs. The reduction was even greater than that observed with aromatase inhibitors, which have generally been found to confer a greater risk reduction than SERMs.

Lasofoxifene selectively binds to both ERα and ERβ with high affinity. Its IC₅₀ for ERα (1.5 nM) is similar to that of estradiol (4.8 nM) and is at least 10-fold higher than those of tamoxifen and raloxifene. Raloxifene also has remarkably improved oral bioavailability relative to tamoxifen and raloxifene, and this may also be involved in its greater potency.