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]
Affected Organisms
Humans and other mammals
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) 8
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
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
CHEMBL489
CAS Number
68047-06-3
UNII
95K54647BZ
DrugBank ID
DB04468
TTD ID
D09NST
VARIDT ID
DR01487
INTEDE ID
DR1944
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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]

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

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]

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]
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]
Adenylate kinase 2, mitochondrial (AK2) OTZG3X2H KAD2_HUMAN Drug Response [8]
Adenylate kinase isoenzyme 5 (AK5) OTTGXLOT KAD5_HUMAN Drug Response [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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) Jump to Detail Molecular Expression Atlas of This Drug

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.