Details of the Drug

General Information of Drug (ID: DMFORDT)

Drug Name

Afimoxifene

Synonyms

4-Hydroxytamoxifen; Afimoxifene; (Z)-4-Hydroxytamoxifen; Hydroxytamoxifen; 4-Monohydroxytamoxifen; Tamogel; 68047-06-3; trans-4-Hydroxytamoxifen; Ici 79280; 68392-35-8; 65213-48-1; 4-OH-TAM; (Z)-4-(1-(4-(2-(Dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenol; Z-4-hydroxytamoxifen; UNII-95K54647BZ; CHEMBL489; ICI 79,280; TAMOXIFEN, 4-HYDROXY-, (Z)-; BRN 4910749; (E/Z)-4-Hydroxy Tamoxifen; MLS000069742; C26H29NO2; CHEBI:44616; 95K54647BZ; SMR000058939; 4-(1-(4-(2-(Dimethylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenol

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[1]
Ductal carcinoma	2E65.2	Phase 2	[2]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

387.5

Logarithm of the Partition Coefficient (xlogp)

6.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is absorbed after topical application []

Chemical Identifiers

Formula: C26H29NO2
IUPAC Name: 4-[(Z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenylbut-1-enyl]phenol
Canonical SMILES: CC/C(=C(\\C1=CC=C(C=C1)O)/C2=CC=C(C=C2)OCCN(C)C)/C3=CC=CC=C3
InChI: InChI=1S/C26H29NO2/c1-4-25(20-8-6-5-7-9-20)26(21-10-14-23(28)15-11-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25-
InChIKey: TXUZVZSFRXZGTL-QPLCGJKRSA-N

Cross-matching ID

PubChem CID: 449459
ChEBI ID: CHEBI:44616
CAS Number: 68047-06-3
DrugBank ID: DB04468
TTD ID: D09NST
VARIDT ID: DR01487
INTEDE ID: DR1944

Repurposed Drugs (RPD)

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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	[3]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[5]
UDP-glucuronosyltransferase 1A8 (UGT1A8)	DE2GB8N	UD18_HUMAN	Substrate	[5]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,4-alpha-glucan-branching enzyme (GBE1)	OTK2N05B	GLGB_HUMAN	Gene/Protein Processing	[6]
14-3-3 protein zeta/delta	OT2TKG9P	1433Z_HUMAN	Gene/Protein Processing	[6]
26S proteasome non-ATPase regulatory subunit 14 (PSMD14)	OTJWHMZ5	PSDE_HUMAN	Gene/Protein Processing	[7]
26S proteasome non-ATPase regulatory subunit 6 (PSMD6)	OTX59EGK	PSMD6_HUMAN	Gene/Protein Processing	[7]
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1)	OTQRET2B	S5A1_HUMAN	Gene/Protein Processing	[6]
4-aminobutyrate aminotransferase, mitochondrial (ABAT)	OTXAGR7J	GABT_HUMAN	Gene/Protein Processing	[6]
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	OT7TNF0L	AAPK1_HUMAN	Drug Response	[8]
60 kDa heat shock protein, mitochondrial (HSPD1)	OTTO1Y11	CH60_HUMAN	Gene/Protein Processing	[7]
Achaete-scute homolog 1 (ASCL1)	OTI4X44G	ASCL1_HUMAN	Gene/Protein Processing	[9]
Adenosine deaminase (ADA)	OTOX2872	ADA_HUMAN	Gene/Protein Processing	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Breast cancer

ICD Disease Classification

2C60-2C65

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
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	7.69E-01	1.91E-02	5.45E-02

Molecular Expression Atlas (MEA)

MEA Detail

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References

1	ClinicalTrials.gov (NCT00272714) Study of Afimoxifene Gel to Treat Cyclic Mastalgia in Premenopausal Women. U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	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).
4	Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
5	Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2006-14.
6	Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
7	Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
8	High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
9	Regulation of aryl hydrocarbon receptor function by selective estrogen receptor modulators. Mol Endocrinol. 2010 Jan;24(1):33-46.