Repositioning Candidate Details
| Candidate ID: | R0941 |
| Source ID: | DB06202 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Lasofoxifene |
| Synonyms: | (-)-cis-5,6,7,8-Tetrahydro-6-phenyl-5-(p-(2-(1-pyrrolidinyl)ethoxy)phenyl)-2-naphthol; Lasofoxifene |
| Molecular Formula: | C28H31NO2 |
| SMILES: | [H][C@@]1(CCC2=CC(O)=CC=C2[C@@]1([H])C1=CC=C(OCCN2CCCC2)C=C1)C1=CC=CC=C1 |
| Structure: |
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| DrugBank Description: | Lasofoxifene is a non-steroidal 3rd generation selective estrogen receptor modulator (SERM) that selectively binds to both ERα and ERβ with high affinity. It is a naphthalene derivative marketed for prevention and treatment of osteoporosis and for the treatment of vaginal atrophy. It was initially developed as Oporia by Pfizer as a treatment for postmenopausal osteoporosis and vaginal atrophy, in which were both rejected for approval by FDA. Later Fablyn was developed as a result of a research collaboration between Pfizer and Ligand Pharmaceuticals with a newly submitted New Drug Application in 2008. It gained approval by European Commission in March 2009. Ligand Pharmaceuticals signed a license agreement with Sermonix Pharmaceuticals for the development and commercialization of oral lasofoxifene in the USA. |
| CAS Number: | 180916-16-9 |
| Molecular Weight: | 413.5512 |
| DrugBank Indication: | Investigated for use/treatment in postmenopausal osteoporosis to reduce the risk of both vertebral and novertebral fractures, as well as address other postmenopausal conditions, including reduction in risk of breast cancer and treatment of vulvar and vaginal atrophy (VVA) |
| DrugBank Pharmacology: | Lasofoxifene exhibits both significant estrogenic and antiestrogenic activity both in vitro and in vivo, targeting any tissues that possess ERs, such as bone, uterus, breast, blood vessels, and liver. Binding assays demonstrated high affinity of the compound for both ERα and ERβ in a tissue-dependent manner. It mimics the effects of estradiol with varying agonist and antagonist effects. |
| DrugBank MoA: | Lasofoxifene mediates an agonist effect on estrogen receptors expressed on bone to mimic the positive effects of estrogen to reduce the production and lifespan of osteoclasts via altering the NF-kappaB ligand (RANKL)/RANK/osteoprotegerin system, stimulation of osteoblast (the bone forming cells) activity and additional effects on calcium homeostasis . It acts as an antagonist at uterus and mammary glands by suppressing the estrogen signaling in oncogenic pathways and inhibits the downstream gene transcription . A study also suggests that lasofoxifene may also act as an inverse agonist at CB2 cannabinoid receptor which is expressed in bone to inhibit osteoclast formation and resorptive activity. |
| Targets: | Estrogen receptor alpha antagonist&agonist&negative modulator; Estrogen receptor beta agonist; Cannabinoid receptor 2 inverse agonist |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I15 | 1290 | Bone disease | A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease | disease of anatomical entity/ musculoskeletal system disease/connective tissue disease | Details |