General
Preferred name
RALOXIFENE
Synonyms
RALOXIFENE HYDROCHLORIDE ()
LY139481 hydrochloride ()
LY156758 hydrochloride ()
Raloxifene HCl ()
LY156758 (Keoxifene) HCl ()
Keoxifene hydrochloride ()
LY156758 (hydrochloride) ()
Evista ()
LY 139481 ()
Keoxifene ()
[2-(4-Hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl][4-(2-(1-piperidinyl)ethoxy)phenyl]methanone ()
Methanone, [6-Hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]- ()
Raloxifene (hydrochloride) ()
LY156758 (free base) ()
LY139481 ()
Keoxifene (hydrochloride) ()
LY156758 ()
LY139481 (hydrochloride) ()
Keoxifene, Pharoxifene, LY-139481, LY-156758, CCRIS-7129 ()
Raloxifene teva ()
Evirex ()
Optruma ()
Ostiral ()
LY-156758 ()
Razylan ()
NSC-706725 ()
Eviden ()
NSC-747974 ()
LY-139481 ()
J22.982B ()
Raloxiphene ()
Raxeto ()
Raloxifene-d4 (hydrochloride) ()
P&D ID
PD004108
CAS
84449-90-1
1020061-04-4
82640-04-8
Tags
probe
natural product
drug
available
Approved by
EMA
FDA
First approval
1997
Drug Status
investigational
approved
Drug indication
Anti-Estrogen
Osteoporosis
Max Phase
Phase 4
Probe info
Probe type
calculated probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
70
No orthogonal probes found
Similar probes
23
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
The average plasma elimination half-life of raloxifene ranges from 27 to 32 hours.[A4977,T28] The prolonged half-life has been attributed to the drug's reversible systemic metabolism and significant enterohepatic cycling.[A4977]
ROE
Raloxifene predominantly undergoes fecal excretion, with less than 0.2% of the dose being excreted in the urine as unchanged form of the compound and less than 6% of the dose being excreted as glucuronide conjugates. Co-administration with [cholestyramine], a bile acid sequestrant, was shown to reduce the enterohepatic recycling of raloxifene by 60%.[T28]
TOXICITY
**LD50 and Overdose**; ; The oral LD50 value in rats is > 5000 mg/kg, which is about 810 times the human dose.[MSDS] In monkeys, no mortality was seen after a single oral dose of 1000 mg/kg.[label] No cases of raloxifene overdose have been reported during clinical trials. A rare postmarketing report of a non-fatal overdose after oral ingestion of 1.5 g has been reported. Common adverse events of leg cramps, hot flushes, and dizziness have been reported with the use of raloxifene at doses of greater than 180 mg. More serious adverse event of venous thromboembolic events were observed with raloxifene.[A721] Two 18-month-old children accidentally ingested 180 mg of raloxifene and symptoms of ataxia, dizziness, vomiting, rash, diarrhea, tremor, flushing, and elevated alkaline phosphatase levels were reported. There is no known antidote for raloxifene. [label] ; ; **Nonclinical Toxicology**; ; In a two-year mouse carcinogenicity study at raloxifene doses that are higher than the human therapeutic doses, there was an increased incidence of benign and malignant ovarian tumors of granulosa or theca cell origin. Another study showed an increased incidence of testicular interstitial cell tumors, prostatic adenomas, adenocarcinomas, and prostatic leiomyoblastoma in male mice receiving doses higher than human therapeutic doses. There was no evidence of the genotoxic potential of raloxifene in bacterial mutagenicity assays, _in vitro_ rat DNA assays, or other _in vitro_ rodent cell line assays. When assessing effects on the reproductive system of male and female rats, raloxifene caused lack of pregnancy and disruptions in estrous cycles and inhibited ovulation at dose of 0.1 to 10 mg/kg/day. Administration of raloxifene during the preimplantation period at doses greater than 0.1 mg/kg resulted in delayed and disrupted embryo implantation, further leading to prolonged gestation and reduced litter size. There were no effects on sperm production or quality or reproductive performance in male rats. The effects on the fertility by raloxifene were reversible.[label] ; ; **Use in special populations**; ; The use of raloxifene in pregnant or nursing women is not advised. Although there are no specific dosing adjustment guidelines, caution should be undertaken when administering raloxifene in geriatric patients or patients with renal or hepatic impairment.[label]
METABOLISM
Raloxifene is reported to undergo metabolism in the intestines and liver devoid of cytochrome P450 pathway.[A4977] It is extensively metabolized, where less than 1% of the total dose exists as unchanged compound.[label] It mainly undergoes first-pass metabolism to form glucuronide conjugates, raloxifene-4'-glucuronide (raloxifene-4'-β-glucuronide), raloxifene-6-glucuronide (raloxifene-6-β-glucuronide), and raloxifene-6,4'-diglucuronide. No other metabolites have been detected in human plasma. The terminal log-linear portions of the plasma concentration curves for raloxifene and the glucuronides are generally parallel. This is consistent with interconversion of raloxifene and the glucuronide metabolites.[label]
DESCRIPTION
Raloxifene is a selective estrogen receptor modulator (SERM).
(GtoPdb)
ABSORPTION
Raloxifene is well absorbed from the gastrointestinal tract, with approximately 60% fo the drug being absorbed following oral administration.[T28] Due to the extensive first-pass hepatic metabolism that involves glucuronide conjugation, the absolute oral bioavailability of raloxifene is about 2%.[T28] Following oral ingestion of a single dose or multiple dose of raloxifen in healthy postmenopausal women, the mean peak plasma concentrations (Cmax) were 0.50 and 1.36 ng/mL, respectively, and the AUC values were 27.2 and 24.2 ngxhr/mL, respectively. The time to reach Cmax following a single or multiple oral doses were 27.7 and 32.5 hours, respectively.[label] Although not clinically significant, oral ingestion of raloxifene with high-fat meals is thought to increase the systemic bioavailability of the drug[A4977] by increasnig the peak plasma concentrations (Cmax) and AUC by 28% and 16%, respectively.[label]
INDICATION
Indicated for the prevention and treatment of osteoporosis in postmenopausal women, as well as prevention and treatment of corticosteroid-induced bone loss.[label]; ; Indicated for the reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis or postmenopausal women with a high risk for invasive breast cancer.[label]
DESCRIPTION
Highly potent and selective covalent PPARgamma antagonist
(Tocris Bioactive Compound Library)
DESCRIPTION
Selective estrogen receptor modulator (SERM)
(Tocriscreen Plus)
DESCRIPTION
Selective estrogen receptor modulator (SERM)
(Tocriscreen Total)
DESCRIPTION
Estrogen receptor modulator; anti-estrogenic drug
(LOPAC library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
5
Organisms
7
Compound Sets
37
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
NURSA ligand set
Prestwick Chemical Library
Probe Miner (suitable probes)
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
Tocriscreen Total
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
69
Molecular Weight
473.17
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
7
Ring Count
5
Aromatic Ring Count
4
cLogP
6.08
TPSA
70.0
Fraction CSP3
0.25
Chiral centers
0.0
Largest ring
6.0
QED
0.32
Structural alerts
2
aggregator (Aggregator Advisor)
Aggregators
aggregator (ZINC)
Aggregators
Related compounds
Custom attributes
(extracted from source data)
Target Type
Nuclear Receptors
Selectivity
ER
Pathway
Endocrinology/Hormones
Metabolism
Neuroscience
Vitamin D Related/Nuclear Receptor
Autophagy
Target
AO
SERM
ESR1, ESR2
Estrogen Receptor/ERR
Estrogen/progestogen Receptor
Primary Target
Estrogen and Related Receptors
MOA
Modulator
ENG Expression Enhancers
ACVRL1 Expression Enhancers
Selective Estrogen Receptor Modulators (SERM)
estrogen receptor antagonist, selective estrogen receptor modulator (SERM)
Member status
virtual
Indication
osteoporosis, breast cancer
Disease Area
orthopedics, oncology
Source data
