Identification
- Summary
Clomifene is a medication used to induce ovulation.
- Brand Names
- Clomid
- Generic Name
- Clomifene
- DrugBank Accession Number
- DB00882
- Background
A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Clomifene (DB00882)
- Weight
- Average: 405.96
Monoisotopic: 405.18594223 - Chemical Formula
- C26H28ClNO
- Synonyms
- 2-(4-(2-chloro-1,2-diphenylethenyl)phenoxy)-N,N-diethylethanamine
- 2-(p-(2-chloro-1,2-diphenylvinyl)phenoxy)triethylamine
- 2-(p-(β-chloro-α-phenylstyryl)phenoxy)triethylamine
- Clomifene
- Clomifeno
- Clomifenum
- Clomiphene
Pharmacology
- Indication
Used mainly in female infertility due to anovulation (e.g. due to polycystic ovary syndrome) to induce ovulation.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Ovulatory dysfunction •••••••••••• - Contraindications & Blackbox Warnings
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Clomifene (previously clomiphene) is an orally administered, non steroidal, ovulatory stimulant that acts as a selective estrogen receptor modulator (SERM). Clomifene can lead to multiple ovulation, and hence increase the risk of conceiving twins. In comparison to purified FSH, the rate of ovarian hyperstimulation syndrome is low. There may be an increased risk of ovarian cancer and weight gain. Clomifene is capable of interacting with estrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with estrogen for estrogen-receptor-binding sites and may delay replenishment of intracellular estrogen receptors. Clomifene initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event, in response to a course of clomifene therapy, is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis resulting in growth of the ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma progesterone and estradiol rise and fall as they would in a normal ovulatory cycle.
- Mechanism of action
Clomifene has both estrogenic and anti-estrogenic properties, but its precise mechanism of action has not been determined. Clomifene appears to stumulate the release of gonadotropins, follicle-stimulating hormone (FSH), and leuteinizing hormone (LH), which leads to the development and maturation of ovarian follicle, ovulation, and subsequent development and function of the coprus luteum, thus resulting in pregnancy. Gonadotropin release may result from direct stimulation of the hypothalamic-pituitary axis or from a decreased inhibitory influence of estrogens on the hypothalamic-pituitary axis by competing with the endogenous estrogens of the uterus, pituitary, or hypothalamus. Clomifene has no apparent progestational, androgenic, or antrandrogenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.
Target Actions Organism AEstrogen receptor alpha antagonistagonistHumans USex hormone-binding globulin Not Available Humans - Absorption
Based on early studies with 14 C-labeled clomifene, the drug was shown to be readily absorbed orally in humans.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic
- Route of elimination
Based on early studies with 14C-labeled clomiphene citrate, the drug was shown to be readily absorbed orally in humans and excreted principally in the feces. Mean urinary excretion was approximately 8% with fecal excretion of about 42%.
- Half-life
5-7 days
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The acute oral LD50 of clomifene is 1700 mg/kg in mice and 5750 mg/kg in rats. The toxic dose in humans is not known. Toxic effects accompanying acute overdosage of clomifene have not been reported. Signs and symptoms of overdosage as a result of the use of more than the recommended dose during clomifene therapy include nausea, vomiting, vasomotor flushes, visual blurring, spots or flashes, scotomata, ovarian enlargement with pelvic or abdominal pain.
- 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
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Clomifene. Abrocitinib The serum concentration of Clomifene can be increased when it is combined with Abrocitinib. Adagrasib The serum concentration of Clomifene can be increased when it is combined with Adagrasib. Afatinib The serum concentration of Clomifene can be increased when it is combined with Afatinib. Ambrisentan The serum concentration of Ambrisentan can be increased when it is combined with Clomifene. - Food Interactions
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Clomifene citrate 1B8447E7YI 50-41-9 PYTMYKVIJXPNBD-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Androxal / Clomifert / Clostilbegyt (Egis) / Omifin (Sanofi)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clomid Tablet 50 mg Oral Sanofi Aventis 1995-12-31 2020-07-15 Canada 
Clomid Tablet 50 mg/1 Oral Sanofi Aventis 1967-02-01 2014-08-21 US 
Clomid 50mg Tablet 50 mg / tab Oral Merrell Pharms Inc., Division Of Merrell Dow (Can) 1967-12-31 1996-09-09 Canada Serophene Tablet 50 mg/1 Oral Emd Serono 1982-03-22 2014-11-30 US Serophene Tablet 50 mg/1 Oral Physicians Total Care, Inc. 1982-03-22 2013-06-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clomid Tablet 50 mg/1 Oral A-S Medication Solutions 2022-09-09 Not applicable US Clomid Tablet 50 mg/1 Oral Cosette Pharmaceuticals, Inc. 2022-09-09 Not applicable US Clomiphene Citrate Tablet 50 mg/1 Oral Par Pharmaceutical, Inc. 1999-08-30 2025-02-28 US Clomiphene Citrate Tablet 50 mg/1 Oral A-S Medication Solutions 1999-08-30 2025-02-28 US 
Clomiphene Citrate Tablet 50 mg/1 Oral Actavis Pharma Company 1990-10-01 2018-06-30 US
Categories
- ATC Codes
- G03GB02 — Clomifene
- Drug Categories
- Benzene Derivatives
- Benzylidene Compounds
- Clomiphene
- Estrogen Agonist-antagonists
- Estrogen Agonist/Antagonist
- Estrogen Antagonists
- Estrogen Receptor Modulators
- Fertility Agents
- Fertility Agents, Female
- Genito Urinary System and Sex Hormones
- Hormone Antagonists
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Ovulation Stimulants, Synthetic
- P-glycoprotein substrates
- Reproductive Control Agents
- Selective Estrogen Receptor Modulators
- Sex Hormones and Modulators of the Genital System
- Stilbenes
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Stilbenes
- Sub Class
- Not Available
- Direct Parent
- Stilbenes
- Alternative Parents
- Diphenylmethanes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Trialkylamines / Vinyl chlorides / Chloroalkenes / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Amine / Aromatic homomonocyclic compound / Benzenoid / Chloroalkene / Diphenylmethane / Ether / Haloalkene / Hydrocarbon derivative / Monocyclic benzene moiety
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- tertiary amine (CHEBI:3752)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1HRS458QU2
- CAS number
- 911-45-5
- InChI Key
- GKIRPKYJQBWNGO-UHFFFAOYSA-N
- InChI
- InChI=1S/C26H28ClNO/c1-3-28(4-2)19-20-29-24-17-15-22(16-18-24)25(21-11-7-5-8-12-21)26(27)23-13-9-6-10-14-23/h5-18H,3-4,19-20H2,1-2H3
- IUPAC Name
- {2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]ethyl}diethylamine
- SMILES
- CCN(CC)CCOC1=CC=C(C=C1)C(=C(Cl)C1=CC=CC=C1)C1=CC=CC=C1
References
- Synthesis Reference
Allen, R.E., Palopoli, F.P., Schumann, E.L. and Van Carnpen, M.G. Jr.; US. Patent 2,914,563; November 24, 1959; assigned to The Wrn. S. Merrell Company.
- General References
- Purvin VA: Visual disturbance secondary to clomiphene citrate. Arch Ophthalmol. 1995 Apr;113(4):482-4. [Article]
- Hayon T, Atlas L, Levy E, Dvilansky A, Shpilberg O, Nathan I: Multifactorial activities of nonsteroidal antiestrogens against leukemia. Cancer Detect Prev. 2003;27(5):389-96. [Article]
- Fritz MA, Holmes RT, Keenan EJ: Effect of clomiphene citrate treatment on endometrial estrogen and progesterone receptor induction in women. Am J Obstet Gynecol. 1991 Jul;165(1):177-85. [Article]
- Hughes E, Brown J, Collins JJ, Vanderkerchove P: Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000057. doi: 10.1002/14651858.CD000057.pub2. [Article]
- Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E: Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD002249. doi: 10.1002/14651858.CD002249.pub4. [Article]
- Authors unspecified: Use of clomiphene citrate in women. Fertil Steril. 2006 Nov;86(5 Suppl 1):S187-93. [Article]
- Homburg R: Oral agents for ovulation induction--clomiphene citrate versus aromatase inhibitors. Hum Fertil (Camb). 2008 Mar;11(1):17-22. doi: 10.1080/14647270701689670. [Article]
- Homburg R: Clomiphene citrate--end of an era? A mini-review. Hum Reprod. 2005 Aug;20(8):2043-51. Epub 2005 May 5. [Article]
- External Links
- Human Metabolome Database
- HMDB0015020
- KEGG Drug
- D07726
- KEGG Compound
- C06917
- PubChem Compound
- 2800
- PubChem Substance
- 46504463
- ChemSpider
- 2698
- 2596
- ChEBI
- 3752
- ChEMBL
- CHEMBL2355051
- Therapeutic Targets Database
- DAP001013
- PharmGKB
- PA449046
- RxList
- RxList Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Clomifene
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Infertility / PCO - Polycystic Ovaries 1 4 Active Not Recruiting Treatment Infertility / Polycystic Ovarian Syndrome (PCOS) 1 4 Completed Not Available Female Infertility 1 4 Completed Diagnostic Ovulatory Dysfunction / Unexplained Infertility 1 4 Completed Supportive Care Polycystic Ovarian Syndrome (PCOS) 1
Pharmacoeconomics
- Manufacturers
- Sanofi aventis us llc
- Par pharmaceutical inc
- Milex products inc
- Emd serono inc
- Packagers
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- EMD Canada Inc.
- Medisca Inc.
- Merrell Pharmaceuticals Inc.
- Nucare Pharmaceuticals Inc.
- Par Pharmaceuticals
- Patheon Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Qualitest
- Rebel Distributors Corp.
- Redpharm Drug
- Sanofi-Aventis Inc.
- Teva Pharmaceutical Industries Ltd.
- Watson Pharmaceuticals
- Dosage Forms
Form Route Strength Tablet Oral 50 mg / tab Tablet Oral Tablet Oral 50 mg/1 Tablet Oral 50.000 mg Tablet Oral 50 mg Capsule - Prices
Unit description Cost Unit ClomiPHENE Citrate 30 50 mg tablet Box 215.9USD box Clomiphene citrate powder 47.74USD g Clomid 50 mg tablet 17.1USD tablet Serophene 50 mg tablet 11.08USD tablet Clomiphene citrate 50 mg tab 6.86USD tablet Clomid 50 mg Tablet 6.09USD tablet Serophene 50 mg Tablet 5.52USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 116.5-118 Allen, R.E., Palopoli, F.P., Schumann, E.L. and Van Carnpen, M.G. Jr.; US. Patent 2,914,563; November 24, 1959; assigned to The Wrn. S. Merrell Company. water solubility Slightly soluble Not Available logP 7.2 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000414 mg/mL ALOGPS logP 6.08 ALOGPS logP 6.47 Chemaxon logS -6 ALOGPS pKa (Strongest Basic) 9.31 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 12.47 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 133.76 m3·mol-1 Chemaxon Polarizability 46.72 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.8723 Caco-2 permeable + 0.7235 P-glycoprotein substrate Substrate 0.7536 P-glycoprotein inhibitor I Inhibitor 0.7799 P-glycoprotein inhibitor II Non-inhibitor 0.6476 Renal organic cation transporter Inhibitor 0.7021 CYP450 2C9 substrate Non-substrate 0.7972 CYP450 2D6 substrate Non-substrate 0.6847 CYP450 3A4 substrate Substrate 0.7021 CYP450 1A2 substrate Inhibitor 0.9332 CYP450 2C9 inhibitor Non-inhibitor 0.6036 CYP450 2D6 inhibitor Inhibitor 0.8315 CYP450 2C19 inhibitor Inhibitor 0.7004 CYP450 3A4 inhibitor Non-inhibitor 0.8089 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9254 Ames test Non AMES toxic 0.5 Carcinogenicity Non-carcinogens 0.621 Biodegradation Not ready biodegradable 0.9895 Rat acute toxicity 1.8805 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.8038 hERG inhibition (predictor II) Inhibitor 0.8672
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 207.1114728 predictedDarkChem Lite v0.1.0 [M-H]- 195.25578 predictedDeepCCS 1.0 (2019) [M+H]+ 206.6991728 predictedDarkChem Lite v0.1.0 [M+H]+ 197.61378 predictedDeepCCS 1.0 (2019) [M+Na]+ 206.5472728 predictedDarkChem Lite v0.1.0 [M+Na]+ 205.46138 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- 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
- Sasson S: Equilibrium binding analysis of estrogen agonists and antagonists: relation to the activation of the estrogen receptor. Pathol Biol (Paris). 1991 Jan;39(1):59-69. [Article]
- Kurosawa T, Hiroi H, Momoeda M, Inoue S, Taketani Y: Clomiphene citrate elicits estrogen agonistic/antagonistic effects differentially via estrogen receptors alpha and beta. Endocr J. 2010;57(6):517-21. Epub 2010 Apr 6. [Article]
- Hughes E, Brown J, Collins JJ, Vanderkerchove P: Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD000057. doi: 10.1002/14651858.CD000057.pub2. [Article]
- Brown J, Farquhar C, Beck J, Boothroyd C, Hughes E: Clomiphene and anti-oestrogens for ovulation induction in PCOS. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD002249. doi: 10.1002/14651858.CD002249.pub4. [Article]
- Authors unspecified: Use of clomiphene citrate in women. Fertil Steril. 2006 Nov;86(5 Suppl 1):S187-93. [Article]
- Overbeek A, Lambalk N: Pharmacogenomics of ovulation induction: facilitating decisions on who, when and how to treat. Pharmacogenomics. 2009 Sep;10(9):1377-9. doi: 10.2217/pgs.09.110. [Article]
- Homburg R: Oral agents for ovulation induction--clomiphene citrate versus aromatase inhibitors. Hum Fertil (Camb). 2008 Mar;11(1):17-22. doi: 10.1080/14647270701689670. [Article]
- Homburg R: Clomiphene citrate--end of an era? A mini-review. Hum Reprod. 2005 Aug;20(8):2043-51. Epub 2005 May 5. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Androgen binding
- Specific Function
- Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid 17-alpha-monooxygenase activity
- Specific Function
- Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation ...
- Gene Name
- CYP17A1
- Uniprot ID
- P05093
- Uniprot Name
- Steroid 17-alpha-hydroxylase/17,20 lyase
- Molecular Weight
- 57369.995 Da
References
- O'Keefe RK, Marrone BL: Inhibition of androgen and oestrogen production by clomiphene citrate in avian theca cells. J Reprod Fertil. 1986 Nov;78(2):541-8. doi: 10.1530/jrf.0.0780541. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Rao US, Fine RL, Scarborough GA: Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55