clomifene 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
antiestrogens or estrogen receptor modulators, clomifene and tamoxifen derivatives 700 911-45-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • clomifene citrate
  • clomifene
  • clomiphene
  • Clomiphene B
  • clomiphene citrate
  • clomid
A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Note that ENCLOMIPHENE and ZUCLOMIPHENE are the (E) and (Z) isomers of Clomiphene respectively.
  • Molecular weight: 405.97
  • Formula: C26H28ClNO
  • CLOGP: 7.15
  • LIPINSKI: 1
  • HAC: 2
  • HDO: 0
  • TPSA: 12.47
  • ALOGS: -5.99
  • ROTB: 9
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
9 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 1.11 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 8 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 3.52 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 93 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.785 Moderate 0.67
caco2-efflux Caco-2 efflux ratio (BA/AB) 3.148 Moderate 0.67
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 1.888 10^-6 cm/s Moderate 0.67
dh-clint Dog hepatocyte intrinsic clearance 30.690 uL/min/10^6 cells Moderate 0.67
dppb Dog plasma protein binding (% unbound) 0.240 % Moderate 0.67
fcs-ppb Fetal calf serum protein binding (% unbound) 0.860 % Moderate 0.67
herg hERG pIC50 5.773 pIC50 Moderate 0.67
hh-clint Human hepatocyte intrinsic clearance 4.178 uL/min/10^6 cells Moderate 0.67
hlm-clint Human liver microsomal intrinsic clearance 13.092 uL/min/mg protein Moderate 0.67
hppb Human plasma protein binding (% unbound) 0.300 % Moderate 0.67
kinase-safety-class ACVR2A,ACVR2B,AKT1,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,JAK3,MAP3K1,MAP3K21,MAP3K7,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,MTOR,NTRK2,PDK2,PDK4,PDPK1,PIK3CB,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,TEK,TTK 48
kinase-selectivity-class GRK2,PDK4 2
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.242 Moderate 0.67
mh-clint Mouse hepatocyte intrinsic clearance 66.374 Moderate 0.67
mppb Mouse plasma protein binding (% unbound) 0.170 Moderate 0.67
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 3.837 Moderate 0.67
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.650 % Moderate 0.67
rh-clint Rat hepatocyte intrinsic clearance 62.517 uL/min/10^6 cells Moderate 0.67
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.320 % Moderate 0.67
rppb Rat plasma protein binding (% unbound) 0.230 % Moderate 0.67
solubility-dd Solubility at pH 7.4 in DMSO 1.858 uM Moderate 0.67

Approvals:

DateAgencyCompanyOrphan
Feb. 1, 1967 FDA SANOFI AVENTIS US
March 11, 2022 PMDA Fuji Pharma Co., Ltd

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Exposure during pregnancy 249.10 33.96 113 1760 238297 90388277
Heterotopic pregnancy 180.09 33.96 19 1854 7 90626567
Abortion spontaneous 173.07 33.96 58 1815 53998 90572576
Ovarian hyperstimulation syndrome 169.46 33.96 36 1837 5826 90620748
Gestational diabetes 98.63 33.96 26 1847 10556 90616018
Multiple pregnancy 96.85 33.96 12 1861 55 90626519
Ectopic pregnancy 94.16 33.96 20 1853 3221 90623353
Adnexal torsion 93.29 33.96 15 1858 519 90626055
Maternal exposure before pregnancy 69.49 33.96 20 1853 11193 90615381
Retinopathy of prematurity 61.69 33.96 10 1863 364 90626210
Abortion 57.52 33.96 13 1860 2782 90623792
Foetal exposure during pregnancy 56.15 33.96 24 1849 42951 90583623
Twin pregnancy 55.71 33.96 11 1862 1232 90625342
Maternal exposure during pregnancy 53.18 33.96 50 1823 360013 90266561
Cleft lip 52.89 33.96 8 1865 184 90626390
Neonatal respiratory distress syndrome 50.89 33.96 12 1861 3089 90623485
Abortion threatened 50.28 33.96 9 1864 594 90625980
Premature baby 50.04 33.96 19 1854 25058 90601516
Pregnancy 44.81 33.96 23 1850 62024 90564550
Ruptured ectopic pregnancy 44.58 33.96 8 1865 535 90626039
Caesarean section 40.42 33.96 15 1858 18562 90608012
Premature delivery 35.81 33.96 17 1856 38745 90587829

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Muscle mass 58.01 36.04 9 861 250 42620215
Foetal exposure during pregnancy 57.65 36.04 25 845 47286 42573179
Testicular atrophy 56.60 36.04 10 860 622 42619843
Hypothalamic pituitary adrenal axis suppression 56.60 36.04 9 861 294 42620171
Cardiac valve fibroelastoma 55.15 36.04 7 863 41 42620424
Toxic cardiomyopathy 46.47 36.04 8 862 427 42620038
Prescription drug used without a prescription 42.01 36.04 10 860 2720 42617745
Hypospadias 39.35 36.04 10 860 3557 42616908
Left ventricular hypertrophy 38.00 36.04 12 858 9307 42611158
Premature baby 37.46 36.04 15 855 23138 42597327

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Heterotopic pregnancy 182.14 27.36 19 2032 7 110587241
Ovarian hyperstimulation syndrome 170.63 27.36 35 2016 5325 110581923
Abortion spontaneous 110.25 27.36 36 2015 34246 110553002
Exposure during pregnancy 106.86 27.36 55 1996 167369 110419879
Gestational diabetes 105.45 27.36 25 2026 7364 110579884
Ectopic pregnancy 97.04 27.36 19 2032 2278 110584970
Multiple pregnancy 92.45 27.36 11 2040 38 110587210
Adnexal torsion 90.45 27.36 14 2037 422 110586826
Twin pregnancy 66.24 27.36 12 2039 946 110586302
Testicular atrophy 54.58 27.36 9 2042 407 110586841
Cardiac valve fibroelastoma 54.48 27.36 7 2044 51 110587197
Abortion threatened 53.54 27.36 9 2042 458 110586790
Muscle mass 53.24 27.36 9 2042 474 110586774
Hypothalamic pituitary adrenal axis suppression 50.14 27.36 9 2042 673 110586575
Maternal exposure before pregnancy 46.58 27.36 13 2038 7252 110579996
Caesarean section 46.35 27.36 15 2036 13802 110573446
Ruptured ectopic pregnancy 46.35 27.36 8 2043 477 110586771
Toxic cardiomyopathy 42.46 27.36 8 2043 781 110586467
Prescription drug used without a prescription 40.63 27.36 11 2040 5485 110581763
Maternal exposure during pregnancy 36.05 27.36 33 2018 254850 110332398
Left ventricular hypertrophy 34.95 27.36 12 2039 13232 110574016
Benign hydatidiform mole 34.31 27.36 5 2046 99 110587149
Premature delivery 31.48 27.36 14 2037 30618 110556630
Cardiac death 30.88 27.36 7 2044 1689 110585559
Myocardial fibrosis 29.75 27.36 7 2044 1988 110585260
Secondary hypogonadism 29.58 27.36 6 2045 857 110586391
Premature rupture of membranes 28.36 27.36 8 2043 4629 110582619

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC G03GB02 GENITO URINARY SYSTEM AND SEX HORMONES
SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
GONADOTROPINS AND OTHER OVULATION STIMULANTS
Ovulation stimulants, synthetic
FDA MoA N0000000168 Selective Estrogen Receptor Modulators
CHEBI has role CHEBI:50739 estrogen receptor modulator
CHEBI has role CHEBI:50837 estrogen antagonist
CHEBI has role CHEBI:50751 anti-estrogen
MeSH PA D004965 Estrogen Antagonists
MeSH PA D005300 Fertility Agents, Female
MeSH PA D006727 Hormone Antagonists
MeSH PA D012102 Reproductive Control Agents
MeSH PA D020845 Selective Estrogen Receptor Modulators
FDA EPC N0000175826 Estrogen Agonist/Antagonist

Related Drugs by ATC class:

G03GB Ovulation stimulants, synthetic 2 drugs
cyclofenilepimestrol

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Female infertility indication 6738008
Ovulation induction indication 61285001
Controlled ovarian stimulation indication 732970000
Induction of spermatogenesis indication
Male infertility off-label use 2904007 DOID:12336
Oligozoospermia off-label use 88311004
Ovarian Function Studies off-label use
Corpus Luteum Insufficiency Syndrome off-label use
Diagonstic Test for Hypothalamic Pituitary Gonadal Axis off-label use
Severe adrenal insufficiency contraindication 24867002
Depressive disorder contraindication 35489007
Hypothyroidism contraindication 40930008 DOID:1459
Thrombophlebitis contraindication 64156001 DOID:3875
Intermenstrual bleeding - irregular contraindication 64996003
Polycystic ovaries contraindication 69878008
Cyst of ovary contraindication 79883001
Thyrotoxicosis contraindication 90739004 DOID:7997
Neoplasm of pituitary gland contraindication 127024001 DOID:1785
Endometriosis contraindication 129103003
Ovarian hyperstimulation syndrome contraindication 129635004 DOID:5425
Disease of liver contraindication 235856003 DOID:409
Endometrial carcinoma contraindication 254878006 DOID:2871
Pregnancy, function contraindication 289908002
Lesion of brain contraindication 301766008
Thromboembolic disorder contraindication 371039008
Visual impairment contraindication 397540003
Visual Disturbance of Seeing Spots contraindication
Scotomata contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.9 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Estrogen receptor Nuclear hormone receptor MODULATOR Ki 8.89 DRUG MATRIX CHEMBL
Alpha-2A adrenergic receptor GPCR Ki 6.46 DRUG MATRIX
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 8.10 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.75 WOMBAT-PK
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase Enzyme Ki 9 CHEMBL
Sodium-dependent serotonin transporter Transporter Ki 6.47 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 6.07 DRUG MATRIX
5-hydroxytryptamine receptor 2A GPCR Ki 6.03 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 6.06 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 6.18 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 5.71 CHEMBL
Alpha-2B adrenergic receptor GPCR Ki 6.14 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 6.35 DRUG MATRIX
Histamine H1 receptor GPCR Ki 5.19 WOMBAT-PK
Muscarinic acetylcholine receptor M1 GPCR Ki 6.41 DRUG MATRIX
Muscarinic acetylcholine receptor M2 GPCR Ki 5.89 DRUG MATRIX
Muscarinic acetylcholine receptor M3 GPCR Ki 6.36 DRUG MATRIX
Muscarinic acetylcholine receptor M4 GPCR Ki 6.64 DRUG MATRIX
Muscarinic acetylcholine receptor M5 GPCR Ki 5.90 DRUG MATRIX
Beta-3 adrenergic receptor GPCR Ki 5.37 DRUG MATRIX
Alpha-2C adrenergic receptor GPCR Ki 6.67 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Ki 6.21 DRUG MATRIX
Cytochrome P450 2D6 Enzyme IC50 5 DRUG MATRIX
Adenosine receptor A3 GPCR Ki 5.52 DRUG MATRIX
Epidermal growth factor receptor Kinase IC50 5.98 DRUG MATRIX
Tyrosine-protein kinase Fyn Kinase IC50 5.60 DRUG MATRIX
Receptor tyrosine-protein kinase erbB-2 Kinase IC50 5.78 DRUG MATRIX
Substance-K receptor GPCR Ki 5.82 DRUG MATRIX
Prostaglandin G/H synthase 1 Enzyme IC50 6.46 DRUG MATRIX
Androgen receptor Transcription factor IC50 4.87 CHEMBL
Alpha-1B adrenergic receptor GPCR Ki 5.60 DRUG MATRIX
Membrane-associated progesterone receptor component 1 Membrane receptor Ki 7.52 DRUG MATRIX
C-8 sterol isomerase Enzyme Ki 6.80 CHEMBL

External reference:

IDSource
4018616 VUID
N0000179535 NUI
D00962 KEGG_DRUG
50-41-9 SECONDARY_CAS_RN
142431 RXNORM
C0009008 UMLSCUI
CHEBI:3752 CHEBI
53Q PDB_CHEM_ID
CHEMBL2355051 ChEMBL_ID
CHEMBL3185958 ChEMBL_ID
DB00882 DRUGBANK_ID
1548955 PUBCHEM_CID
356 MMSL
362 MMSL
4475 MMSL
d00569 MMSL
002101 NDDF
004781 NDDF
30466001 SNOMEDCT_US
387166005 SNOMEDCT_US
387346007 SNOMEDCT_US
D002996 MESH_DESCRIPTOR_UI
4159 IUPHAR_LIGAND_ID
1309 INN_ID
4018616 VANDF
4019686 VANDF
1HRS458QU2 UNII
1HRS458QU2 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Clomid HUMAN PRESCRIPTION DRUG LABEL 1 0713-0885 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 16729-723 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 21695-114 TABLET 50 mg ORAL ANDA 18 sections
MiloPhene HUMAN PRESCRIPTION DRUG LABEL 1 35573-470 TABLET 50 mg ORAL ANDA 17 sections
MiloPhene HUMAN PRESCRIPTION DRUG LABEL 1 35573-470 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 50090-0677 TABLET 50 mg ORAL NDA authorized generic 22 sections
CLOMID HUMAN PRESCRIPTION DRUG LABEL 1 50090-6500 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate Human Prescription Drug Label 1 52343-557 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 54868-3059 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate Human Prescription Drug Label 1 55801-187 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate Human Prescription Drug Label 1 64980-690 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 68071-2638 TABLET 50 mg ORAL ANDA 17 sections
Clomiphene citrate Human Prescription Drug Label 1 70954-825 TABLET 50 mg ORAL ANDA 20 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 72888-213 TABLET 50 mg ORAL ANDA 13 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 72888-213 TABLET 50 mg ORAL ANDA 13 sections
Clomiphene Citrate HUMAN PRESCRIPTION DRUG LABEL 1 83390-107 TABLET 50 mg ORAL ANDA 17 sections