Details of the Drug

General Information of Drug (ID: DMWTAOI)

Drug Name
Estramustine
Synonyms
Estramustina; Estramustinum; Emcyt (TN); Estramustine (USAN/INN); Estradiol 3-[bis(2-chloroethyl)carbamate]; Ro-22-2296/000; Estra-1,3,5(10)-triene-3,17-diol (17.beta.)-, 3-[bis(2-chloroethyl)carbamate]; [(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] N,N-bis(2-chloroethyl)carbamate; (17beta)-17-hydroxyestra-1(10),2,4-trien-3-yl bis(2-chloroethyl)carbamate; 17.beta.-Estradiol 3-[bis(2-chloroethyl)carbamate]
Indication
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Approved [1]
Therapeutic Class
Anticancer Agents
Affected Organisms
Humans and other mammals
ATC Code
L01XX11: Estramustine
L01XX: Other antineoplastic agents
L01X: OTHER ANTINEOPLASTIC AGENTS
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 440.4
Logarithm of the Partition Coefficient (xlogp) 4
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Clearance
The drug present in the plasma can be removed from the body at the rate of 0.94 mL/min/kg [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 20 hours [2]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 16.4712 micromolar/kg/day [3]
Unbound Fraction
The unbound fraction of drug in plasma is 0.5% [2]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.12 L/kg [2]
Chemical Identifiers
Formula
C23H31Cl2NO3
IUPAC Name
[(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] N,N-bis(2-chloroethyl)carbamate
Canonical SMILES
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4)OC(=O)N(CCCl)CCCl
InChI
InChI=1S/C23H31Cl2NO3/c1-23-9-8-18-17-5-3-16(29-22(28)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)27/h3,5,14,18-21,27H,2,4,6-13H2,1H3/t18-,19-,20+,21+,23+/m1/s1
InChIKey
FRPJXPJMRWBBIH-RBRWEJTLSA-N
Cross-matching ID
PubChem CID
259331
ChEBI ID
CHEMBL1575
CAS Number
2998-57-4
UNII
35LT29625A
DrugBank ID
DB01196
TTD ID
D03SRY
VARIDT ID
DR00522
INTEDE ID
DR0645
ACDINA ID
D00247
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
Estramustine binding protein (EMBP) TTSBFYK NOUNIPROTAC Binder [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Keratin, type I cytoskeletal 18 (KRT18) OTVLQFIP K1C18_HUMAN Gene/Protein Processing [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Estramustine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Givosiran DM5PFIJ Moderate Increased risk of nephrotoxicity by the combination of Estramustine and Givosiran. Inborn porphyrin/heme metabolism error [5C58] [7]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive immunosuppressive effects by the combination of Estramustine and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [8]
Plazomicin DMKMBES Moderate Increased risk of nephrotoxicity by the combination of Estramustine and Plazomicin. Urinary tract infection [GC08] [7]

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

DIG
DIG Name DIG ID PubChem CID Functional Classification
Sodium lauryl sulfate E00464 3423265 Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Magnesium stearate E00208 11177 lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Estramustine 140 mg capsule 140 mg Oral Capsule Oral
Estramustine Phosphate Sodium eq 140mg phosphate capsule eq 140mg phosphate Capsule Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 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
4 Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
5 Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. J Urol. 2003 May;169(5):1729-34.
6 Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
7 Cerner Multum, Inc. "Australian Product Information.".
8 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.