NAV

Ormeloxifene

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Ormeloxifene is a selective estrogen receptor modulator used as a non-hormonal, non-steroidal oral contraceptive.

Generic Name
Ormeloxifene
DrugBank Accession Number
DB13310
Background

Ormeloxifene is a third-generation selective estrogen receptor (ER) modulator. In India, ormeloxifene has been marketed since the 1990s as a non-hormonal, non-steroidal oral contraceptive taken once a week,1 and it was later introduced for the treatment of dysfunctional uterine bleeding.4 Similar to other selective estrogen receptor modulators (SERMs), ormeloxifene has estrogenic activity in the vagina, bone, cardiovascular, and central nervous system tissues, and anti-estrogenic activity in the uterus and breast.1,3 The use of ormeloxifene for the treatment of perimenopausal bleeding and the management of menorrhagia has also been investigated.1,2 Ormeloxifene is marketed in India as a racemic mixture of the l- (levormeloxifene) and d-isomers (d-ormeloxifene) of trans-ormeloxifene.5 The use of levormeloxifene for the treatment of reduced bone turnover and the prevention of atherosclerosis has been evaluated; however, drug development was discontinued due to adverse events.6

Type
Small Molecule
Groups
Experimental
Structure
3D
Similar Structures
Weight
Average: 457.614
Monoisotopic: 457.261693991
Chemical Formula
C30H35NO3
Synonyms
  • Centchroman
  • Ormeloxifene
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Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Ormeloxifene is a selective estrogen receptor modulator (SERMs) with contraceptive activity. Also, it has been suggested that it may be beneficial in the treatment of breast cancer, osteoporosis, dermatitis, restenosis, endometriosis and uterine fibroids.4

Mechanism of action

Ormeloxifene has both estrogenic and anti-estrogenic activity. As a contraceptive, ormeloxifene inhibits endometrial receptivity to blastocyst signals. This mechanism inhibits implantation without affecting nidatory estrogen and progesterone, the hypothalamo-pituitary-ovarian axis, follicle maturation, ovulation, mating behavior, gamete transport or fertilization, and the preimplantation development of embryos.4

TargetActionsOrganism
UEstrogen receptor alpha
modulator
Humans
UEstrogen receptor beta
modulator
Humans
Absorption

In healthy, non-lactating volunteers given 30 mg of ormeloxifene (n=11), the Cmax, tmax and AUC0-∞ were 55.5 ng/mL, 5.2 h, and 5199 ng⋅h/mL, respectively.4

Volume of distribution

In healthy women, the apparent volume of distribution (Vd/F) was higher than the total body fluid, and the nursing state does not have an effect on this parameter.4

Protein binding

Approximately 90% of ormeloxifene is bound to albumin.4

Metabolism

In vivo studies suggest that ormeloxifene is quickly metabolized by the liver.8 In rats, the active metabolite of this drug is 7-desmethylated ormeloxifene.8

Route of elimination

In vivo studies suggest that ormeloxifene is excreted from the body primarily via feces.8

Half-life

In healthy, non-lactating volunteers given 30 mg of ormeloxifene (n=11), the half-life is 165 h.4

Clearance

In healthy, non-lactating volunteers given 30 mg of ormeloxifene (n=11), the clearance is 0.14 L/h.4

Adverse Effects
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Toxicity

Toxicity information regarding ormeloxifene is not readily available. Patients experiencing an overdose are at an increased risk of severe cardiovascular adverse effects.7 Symptomatic and supportive measures are recommended.

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AbciximabThe risk or severity of adverse effects can be increased when Ormeloxifene is combined with Abciximab.
AcenocoumarolThe risk or severity of adverse effects can be increased when Ormeloxifene is combined with Acenocoumarol.
AcetaminophenThe metabolism of Ormeloxifene can be increased when combined with Acetaminophen.
AcetazolamideThe metabolism of Ormeloxifene can be increased when combined with Acetazolamide.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Ormeloxifene.
Food Interactions
Not Available

Categories

ATC Codes
G03XC04 — Ormeloxifene
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 7-o-methylated isoflavonoids. These are isoflavonoids with methoxy groups attached to the C7 atom of the isoflavonoid backbone. Isoflavonoids are natural products derived from 3-phenylchromen-4-one.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Isoflavonoids
Sub Class
O-methylated isoflavonoids
Direct Parent
7-O-methylated isoflavonoids
Alternative Parents
Neoflavans / Isoflavans / Stilbenes / 2,2-dimethyl-1-benzopyrans / Phenoxy compounds / Anisoles / Alkyl aryl ethers / N-alkylpyrrolidines / Trialkylamines / Oxacyclic compounds
show 3 more
Substituents
1-benzopyran / 2,2-dimethyl-1-benzopyran / 7-methoxyisoflavonoid-skeleton / Alkyl aryl ether / Amine / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzopyran
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
44AXY5VE90
CAS number
31477-60-8
InChI Key
XZEUAXYWNKYKPL-WDYNHAJCSA-N
InChI
InChI=1S/C30H35NO3/c1-30(2)29(23-9-5-4-6-10-23)28(26-16-15-25(32-3)21-27(26)34-30)22-11-13-24(14-12-22)33-20-19-31-17-7-8-18-31/h4-6,9-16,21,28-29H,7-8,17-20H2,1-3H3/t28-,29+/m1/s1
IUPAC Name
1-(2-{4-[(3R,4R)-7-methoxy-2,2-dimethyl-3-phenyl-3,4-dihydro-2H-1-benzopyran-4-yl]phenoxy}ethyl)pyrrolidine
SMILES
[H][C@@]1(C2=CC=C(OCCN3CCCC3)C=C2)C2=C(OC(C)(C)[C@@]1([H])C1=CC=CC=C1)C=C(OC)C=C2

References

General References
  1. Pati T, Chanania K, Marandi S, Hansa J: Ormeloxifene - Looking beyond contraception. J Midlife Health. 2017 Jan-Mar;8(1):17-20. doi: 10.4103/jmh.JMH_71_16. [Article]
  2. Kriplani A, Kulshrestha V, Agarwal N: Efficacy and safety of ormeloxifene in management of menorrhagia: a pilot study. J Obstet Gynaecol Res. 2009 Aug;35(4):746-52. doi: 10.1111/j.1447-0756.2008.00987.x. [Article]
  3. Chang BY, Kim SA, Malla B, Kim SY: The Effect of Selective Estrogen Receptor Modulators (SERMs) on the Tamoxifen Resistant Breast Cancer Cells. Toxicol Res. 2011 Jun;27(2):85-93. doi: 10.5487/TR.2011.27.2.085. [Article]
  4. Lal J: Clinical pharmacokinetics and interaction of centchroman--a mini review. Contraception. 2010 Apr;81(4):275-80. doi: 10.1016/j.contraception.2009.11.007. Epub 2010 Jan 4. [Article]
  5. Holm P, Shalmi M, Korsgaard N, Guldhammer B, Skouby SO, Stender S: A partial estrogen receptor agonist with strong antiatherogenic properties without noticeable effect on reproductive tissue in cholesterol-fed female and male rabbits. Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):2264-72. doi: 10.1161/01.atv.17.10.2264. [Article]
  6. Ravn P, Nielsen TF, Christiansen C: What can be learned from the levormeloxifene experience? Acta Obstet Gynecol Scand. 2006;85(2):135-42. doi: 10.1080/00016340500345691. [Article]
  7. Bhalla H, Pant KK, Dikshit M, Surin WR, Singh MM: Effect of ormeloxifene, a nonsteroidal once-a-week oral contraceptive, on systemic hemodynamics in adult female rats. J Pharmacol Pharmacother. 2011 Apr;2(2):90-4. doi: 10.4103/0976-500X.81898. [Article]
  8. Gara RK, Sundram V, Chauhan SC, Jaggi M: Anti-cancer potential of a novel SERM ormeloxifene. Curr Med Chem. 2013;20(33):4177-84. doi: 10.2174/09298673113209990197. [Article]
ChemSpider
32935
BindingDB
50219398
ChEMBL
CHEMBL301327
ZINC
ZINC000001730388
Wikipedia
Ormeloxifene

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000102 mg/mLALOGPS
logP6.75ALOGPS
logP6.03Chemaxon
logS-6.6ALOGPS
pKa (Strongest Basic)9Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area30.93 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity137.19 m3·mol-1Chemaxon
Polarizability53.21 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-2116900000-e86d2a9274cd9317239a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0000900000-78e77c47c7eb535597eb
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001l-4439200000-9b085271b903a562eefe
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a6r-0009600000-0365e2693dd3fc968842
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-053r-9410000000-e7caf70f8b33c3e3a791
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-1009100000-995a5a94350ebe044736
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-228.8877146
predicted
DarkChem Lite v0.1.0
[M-H]-211.43753
predicted
DeepCCS 1.0 (2019)
[M+H]+228.9450146
predicted
DarkChem Lite v0.1.0
[M+H]+214.73512
predicted
DeepCCS 1.0 (2019)
[M+Na]+229.1690146
predicted
DarkChem Lite v0.1.0
[M+Na]+222.1035
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. Estrogen receptor alpha
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Awasthi S, Blesson CS, Dwivedi A: Expression of oestrogen receptors alpha and beta during the period of uterine receptivity in rat: effect of ormeloxifene, a selective oestrogen receptor modulator. Acta Physiol (Oxf). 2007 Jan;189(1):47-56. doi: 10.1111/j.1748-1716.2006.01638.x. [Article]
  2. Pati T, Chanania K, Marandi S, Hansa J: Ormeloxifene - Looking beyond contraception. J Midlife Health. 2017 Jan-Mar;8(1):17-20. doi: 10.4103/jmh.JMH_71_16. [Article]
Details2. Estrogen receptor beta
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. Awasthi S, Blesson CS, Dwivedi A: Expression of oestrogen receptors alpha and beta during the period of uterine receptivity in rat: effect of ormeloxifene, a selective oestrogen receptor modulator. Acta Physiol (Oxf). 2007 Jan;189(1):47-56. doi: 10.1111/j.1748-1716.2006.01638.x. [Article]
  2. Pati T, Chanania K, Marandi S, Hansa J: Ormeloxifene - Looking beyond contraception. J Midlife Health. 2017 Jan-Mar;8(1):17-20. doi: 10.4103/jmh.JMH_71_16. [Article]

Carriers

Details1. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Lal J: Clinical pharmacokinetics and interaction of centchroman--a mini review. Contraception. 2010 Apr;81(4):275-80. doi: 10.1016/j.contraception.2009.11.007. Epub 2010 Jan 4. [Article]

Drug created at June 23, 2017 20:39 / Updated at December 01, 2022 11:28