Details of the Drug

General Information of Drug (ID: DM0YZC6)

Drug Name
Fulvestrant
Synonyms
Faslodex; AstraZeneca brand of fulvestrant; Fulvestrant [USAN]; Ici 182780; ZD 182780; ZM 182780; Faslodex (TN); ZD-182780; ZD-9238; ZM-182780; Faslodex(ICI 182,780); Faslodex, ICI 182780, Fulvestrant; Fulvestrant (JAN/USAN/INN); (7R,13S,17S)-13-methyl-7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3,17-diol; (7R,8R,9S,13S,14S,17S)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol; (7R,8S,9S,13S,14S,17S)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl) nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol; (7alpha,17beta)-7-{9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl}estra-1,3,5(10)-triene-3,17-diol; 7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)estra-1,3,5(10)-triene-3,17-diol; 7alpha-(9-((4,4,5,5,5,-Pentafluoropentyl)sulfinyl)nonyl)estra-1,3,5(10)-triene-3,17beta-diol; 7alpha-(9-((4,4,5,5,5-Pentafluoropentyl)sulfinyl)nonyl)estra-1,3,5(10)-triene-3,17beta-diol; 7alpha-[9[(4,4,5,5,5-Pentafluropentyl)sulfinyl]nonyl]-estra-1,3,5(10)-triene-3, 17 beta diol; ICI
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1]
Therapeutic Class
Anticancer Agents
Affected Organisms
Humans and other mammals
ATC Code
L02BA03: Fulvestrant
L02BA: Anti-estrogens
L02B: HORMONE ANTAGONISTS AND RELATED AGENTS
L02: ENDOCRINE THERAPY
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 606.8
Logarithm of the Partition Coefficient (xlogp) 9.2
Rotatable Bond Count (rotbonds) 14
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 9
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Clearance
The drug present in the plasma can be removed from the body at the rate of 11.8 mL/min/kg [3]
Elimination
0.1% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 40 days [3]
Metabolism
The drug is metabolized via the liver []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.00023 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.01% [3]
Vd
The volume of distribution (Vd) of drug is 3-5 L/kg []
Water Solubility
The ability of drug to dissolve in water is measured as 0.001 mg/mL [2]
Chemical Identifiers
Formula
C32H47F5O3S
IUPAC Name
(7R,8R,9S,13S,14S,17S)-13-methyl-7-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
Canonical SMILES
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)[C@@H](CC4=C3C=CC(=C4)O)CCCCCCCCCS(=O)CCCC(C(F)(F)F)(F)F
InChI
InChI=1S/C32H47F5O3S/c1-30-17-15-26-25-12-11-24(38)21-23(25)20-22(29(26)27(30)13-14-28(30)39)10-7-5-3-2-4-6-8-18-41(40)19-9-16-31(33,34)32(35,36)37/h11-12,21-22,26-29,38-39H,2-10,13-20H2,1H3/t22-,26-,27+,28+,29-,30+,41?/m1/s1
InChIKey
VWUXBMIQPBEWFH-WCCTWKNTSA-N
Cross-matching ID
PubChem CID
104741
ChEBI ID
CHEMBL1358
CAS Number
129453-61-8
UNII
22X328QOC4
DrugBank ID
DB00947
TTD ID
D0JO7Y
INTEDE ID
DR0756
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD 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 Antagonist [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [6]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [7]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
2-aminoethanethiol dioxygenase (ADO) OTRLGQ7V AEDO_HUMAN Post-Translational Modifications [8]
2-oxoglutarate dehydrogenase complex component E1 (OGDH) OTHGTQWF ODO1_HUMAN Post-Translational Modifications [8]
24-hydroxycholesterol 7-alpha-hydroxylase (CYP39A1) OTBAJT4I CP39A_HUMAN Post-Translational Modifications [8]
26S proteasome complex subunit SEM1 (SEM1) OTASLBM1 SEM1_HUMAN Post-Translational Modifications [8]
26S proteasome non-ATPase regulatory subunit 14 (PSMD14) OTJWHMZ5 PSDE_HUMAN Gene/Protein Processing [9]
26S proteasome non-ATPase regulatory subunit 6 (PSMD6) OTX59EGK PSMD6_HUMAN Gene/Protein Processing [9]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1) OTNAZVKB 3BHS1_HUMAN Post-Translational Modifications [8]
3',5'-cyclic-AMP phosphodiesterase 4D (PDE4D) OT1RWFV0 PDE4D_HUMAN Post-Translational Modifications [8]
3-hydroxyisobutyrate dehydrogenase, mitochondrial (HIBADH) OTCMMMIZ 3HIDH_HUMAN Post-Translational Modifications [8]
5-hydroxytryptamine receptor 5A (HTR5A) OTRKPCQV 5HT5A_HUMAN Post-Translational Modifications [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
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 7.69E-01 1.91E-02 5.45E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 9.85E-01 2.24E-02 7.33E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Fulvestrant (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Omacetaxine mepesuccinate DMPU2WX Moderate Additive myelosuppressive effects by the combination of Fulvestrant and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [10]

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: 1015).
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 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
5 Beta3-tubulin is induced by estradiol in human breast carcinoma cells through an estrogen-receptor dependent pathway. Cell Motil Cytoskeleton. 2009 Jul;66(7):378-88.
6 Fulvestrant: pharmacologic profile versus existing endocrine agents for the treatment of breast cancer. Ann Pharmacother. 2006 Sep;40(9):1572-83.
7 Inactivation of the pure antiestrogen fulvestrant and other synthetic estrogen molecules by UDP-glucuronosyltransferase 1A enzymes expressed in breast tissue. Mol Pharmacol. 2006 Mar;69(3):908-20.
8 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
9 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.
10 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.