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]
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Therapeutic Class

Anticancer 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: CHEBI:4868
CAS Number: 2998-57-4
DrugBank ID: DB01196
TTD ID: D03SRY
VARIDT ID: DR00522
INTEDE ID: DR0645
ACDINA ID: D00247

Combinatorial Drugs (CBD)

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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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[5]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Post-Translational Modifications	[6]
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Gene/Protein Processing	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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]	[8]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Estramustine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[9]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Estramustine and Plazomicin.	Urinary tract infection [GC08]	[8]
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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
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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

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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	Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2. J Neurooncol. 2001 Aug;54(1):23-9. doi: 10.1023/a:1012566601485.
7	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.
8	Cerner Multum, Inc. "Australian Product Information.".
9	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.