Details of the Drug

General Information of Drug (ID: DMKI7RB)

Drug Name

Clomifene

Synonyms

Androxal; Chlomaphene; Chloramifene; Cisclomifenum; Cisclomiphene; Clomifen; Clomifeno; Clomifenum; Clomifert; Clomiphene; Clostilbegit; Enclomifene; Enclomifeno; Enclomifenum; Enclomiphen; Enclomiphene; Klostilbegit; Transclomifenum; Transclomiphene; Zuclomifene; Zuclomifeno; Zuclomifenum; Zuclomiphene; Clomiphene B;Enclomiphene [USAN]; ISOMER B; Zuclomiphene [USAN]; Cis-Clomifene; Cis-Clomiphene; Clomid (TN); Clomifene (INN); Clomifene (TN); Clomifene [INN:BAN]; Clomifeno [INN-Spanish]; Clomifenum [INN-Latin]; En-Clomiphene; Enclomifeno [INN-Spanish]; Enclomifenum [INN-Latin]; Enclomiphene (USAN); Milophene (TN); RMI 16,289; RMI-16289; RMI-16312; Serophene (TN); Trans-Clomifene; Trans-Clomiphene; Zuclomifeno [INN-Spanish]; Zuclomifenum [INN-Latin]; Zuclomiphene (USAN); Cis-2-(p-(2-Chloro-1,2-diphenylvinyl)phenoxy)triethylamine; Trans-2-(p-(2-Chloro-1,2-diphenylvinyl)phenoxy)triethylamine; Cis-2-(4-(2-Chloro-1,2-diphenylethenyl)phenoxy)-N,N-diethylethanamine; Trans-2-(4-(2-Chloro-1,2-diphenylethenyl)phenoxy)-N,N-diethylethanamine; (E)-2-(p-(2-Chloro-1,2-diphenylvinyl)phenoxy)triethylamine; (Z)-2-(p-(2-Chloro-1,2-diphenylvinyl)phenoxy)triethylamine; (Z)-isomer; 1-(p-(beta-Diethylaminoethoxy)-phenyl)-1,2-diphenylchloroethylene; 2-(4-(2-Chloro-1,2-diphenylethenyl)phenoxy)-N,N-diethylethanamine; 2-(p-(2-Chloro-1,2-diphenylvinyl)phenoxy)triethylamine; 2-(p-(beta-Chloro-alpha-phenylstyryl)phenoxy)-triethylamine; 2-(p-(beta-chloro-alpha-phenylstyryl)phenoxy)triethylamine; 2-({4-[(Z)-2-chloro-1,2-diphenylethenyl]phenyl}oxy)-N,N-diethylethanamine; 2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanamine; 2-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine; 2-[4-[(Z)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine; 2-{4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy}-N,N-diethylethanamine

Indication

Disease Entry	ICD 11	Status	REF
Female infertility	GA31.Z	Approved	[1], [2]

Therapeutic Class

Fertility Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

406

Topological Polar Surface Area (xlogp)

7.2

Rotatable Bond Count (rotbonds)

9

Hydrogen Bond Donor Count (hbonddonor)

0

Hydrogen Bond Acceptor Count (hbondacc)

2

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability: 90% of drug becomes completely available to its intended biological destination(s) [4]
Elimination: 8% of drug is excreted from urine in the unchanged form [3]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.519 micromolar/kg/day [5]
Water Solubility: The ability of drug to dissolve in water is measured as 1.11 mg/mL [3]

Chemical Identifiers

Formula: C26H28ClNO
IUPAC Name: 2-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine
Canonical SMILES: CCN(CC)CCOC1=CC=C(C=C1)/C(=C(\\C2=CC=CC=C2)/Cl)/C3=CC=CC=C3
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/b26-25+
InChIKey: GKIRPKYJQBWNGO-OCEACIFDSA-N

Cross-matching ID

PubChem CID: 1548953
ChEBI ID: CHEBI:3752
CAS Number: 15690-57-0
DrugBank ID: DB06735
TTD ID: D0CT9Y
VARIDT ID: DR01391
INTEDE ID: DR0577
ACDINA ID: D00138

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[6]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)_{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[8]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Female infertility

ICD Disease Classification

GA31.Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.23E-01	-8.20E-02	-3.22E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.95E-01	-7.47E-02	-2.45E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Saccharose	E00091	5988	Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
--------------------

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Clomifene 50 mg tablet	50 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7619).
2	Emerging drugs for hypogonadism. Expert Opin Emerg Drugs. 2006 Nov;11(4):685-707.
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	The future of the new selective estrogen receptor modulators. Menopause Int. 2007 Mar;13(1):27-34.
7	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
8	CYP2D6 is primarily responsible for the metabolism of clomiphene. Drug Metab Pharmacokinet. 2008;23(2):101-5.
9	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
10	Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
11	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
12	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
13	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
14	Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
15	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
16	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
17	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
18	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
19	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
20	MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
21	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
22	Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
23	Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
24	Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
25	Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
26	Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
27	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
28	17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
29	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 620).
30	Clinical pipeline report, company report or official report of Shionogi (2011).
31	Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithe... Prostate Cancer Prostatic Dis. 2009;12(4):375-81.