Thiorphan - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (1)

Targets (1)Biointeractions (1)

Identification

Name

Thiorphan

Accession Number

DB08626 (DB01654)

Type

Small Molecule

Groups

Experimental

Description

A potent inhibitor of membrane metalloendopeptidase (enkephalinase). Thiorphan potentiates morphine-induced analgesia and attenuates naloxone-precipitated withdrawal symptoms.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Not Available

External IDs

Not Available

Product Ingredients

Not Available

Approved Prescription Products

Not Available

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Not Available

Brand mixtures

Not Available

Categories

UNII

B79L7B5X3Z

CAS number

76721-89-6

Weight

Average: 253.317
Monoisotopic: 253.077264041

Chemical Formula

C₁₂H₁₅NO₃S

InChI Key

LJJKNPQAGWVLDQ-SNVBAGLBSA-N

InChI

InChI=1S/C12H15NO3S/c14-11(15)7-13-12(16)10(8-17)6-9-4-2-1-3-5-9/h1-5,10,17H,6-8H2,(H,13,16)(H,14,15)/t10-/m1/s1

IUPAC Name

2-[(2S)-2-benzyl-3-sulfanylpropanamido]acetic acid

SMILES

[H][C@](CS)(CC1=CC=CC=C1)C(=O)NCC(O)=O

Pharmacology

Indication

Not Available

Structured Indications

Not Available

Pharmacodynamics

Not Available

Mechanism of action

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Neprilysin	Protein	unknown	inhibitor	Human	P08473	details

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Abacavir	The serum concentration of Abacavir can be decreased when it is combined with Thiorphan.	Approved, Investigational
Alfuzosin	The serum concentration of Alfuzosin can be increased when it is combined with Thiorphan.	Approved, Investigational
Alprazolam	The serum concentration of Alprazolam can be increased when it is combined with Thiorphan.	Approved, Illicit, Investigational
Ambroxol acefyllinate	The serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Thiorphan.	Experimental
Amineptine	The serum concentration of Amineptine can be increased when it is combined with Thiorphan.	Illicit, Withdrawn
Aminophylline	The serum concentration of Aminophylline can be decreased when it is combined with Thiorphan.	Approved
Amitriptyline	The serum concentration of Amitriptyline can be increased when it is combined with Thiorphan.	Approved
Atorvastatin	The serum concentration of Atorvastatin can be increased when it is combined with Thiorphan.	Approved
Boceprevir	The serum concentration of Thiorphan can be decreased when it is combined with Boceprevir.	Approved, Investigational
Bromocriptine	The serum concentration of Bromocriptine can be increased when it is combined with Thiorphan.	Approved, Investigational
Cabergoline	The serum concentration of Cabergoline can be increased when it is combined with Thiorphan.	Approved
Carbamazepine	The metabolism of Thiorphan can be increased when combined with Carbamazepine.	Approved, Investigational
Chlorotrianisene	The serum concentration of Chlorotrianisene can be decreased when it is combined with Thiorphan.	Withdrawn
Cisapride	The serum concentration of Cisapride can be increased when it is combined with Thiorphan.	Approved, Investigational, Withdrawn
Clarithromycin	The therapeutic efficacy of Clarithromycin can be decreased when used in combination with Thiorphan.	Approved
Clomipramine	The serum concentration of Clomipramine can be increased when it is combined with Thiorphan.	Approved, Vet Approved
Conjugated estrogens	The serum concentration of Conjugated Equine Estrogens can be decreased when it is combined with Thiorphan.	Approved
Cyclobenzaprine	The serum concentration of Cyclobenzaprine can be increased when it is combined with Thiorphan.	Approved
Cyclophosphamide	The risk or severity of adverse effects can be increased when Thiorphan is combined with Cyclophosphamide.	Approved, Investigational
Cyclosporine	The serum concentration of Cyclosporine can be increased when it is combined with Thiorphan.	Approved, Investigational, Vet Approved
Delavirdine	The serum concentration of Delavirdine can be decreased when it is combined with Thiorphan.	Approved
Desipramine	The serum concentration of Desipramine can be increased when it is combined with Thiorphan.	Approved
Dienestrol	The serum concentration of Dienestrol can be decreased when it is combined with Thiorphan.	Approved
Diethylstilbestrol	The serum concentration of Diethylstilbestrol can be decreased when it is combined with Thiorphan.	Approved
Digoxin	The serum concentration of Digoxin can be increased when it is combined with Thiorphan.	Approved
Dihydroergotamine	The serum concentration of Dihydroergotamine can be increased when it is combined with Thiorphan.	Approved
Diltiazem	The metabolism of Diltiazem can be decreased when combined with Thiorphan.	Approved
Dosulepin	The serum concentration of Dosulepin can be increased when it is combined with Thiorphan.	Approved
Doxepin	The serum concentration of Doxepin can be increased when it is combined with Thiorphan.	Approved
Dyphylline	The serum concentration of Dyphylline can be decreased when it is combined with Thiorphan.	Approved
Enfuvirtide	The serum concentration of Enfuvirtide can be increased when it is combined with Thiorphan.	Approved, Investigational
Ergoloid mesylate	The serum concentration of Ergoloid mesylate can be increased when it is combined with Thiorphan.	Approved
Ergonovine	The serum concentration of Ergonovine can be increased when it is combined with Thiorphan.	Approved
Ergotamine	The serum concentration of Ergotamine can be increased when it is combined with Thiorphan.	Approved
Esmirtazapine	The serum concentration of Esmirtazapine can be increased when it is combined with Thiorphan.	Investigational
Estradiol	The serum concentration of Estradiol can be decreased when it is combined with Thiorphan.	Approved, Investigational, Vet Approved
Estramustine	The serum concentration of Estramustine can be decreased when it is combined with Thiorphan.	Approved
Estrogens, esterified	The serum concentration of Estrogens, esterified can be decreased when it is combined with Thiorphan.	Approved
Estrone sulfate	The serum concentration of Estrone sulfate can be decreased when it is combined with Thiorphan.	Approved
Ethinyl Estradiol	The serum concentration of Ethinyl Estradiol can be decreased when it is combined with Thiorphan.	Approved
Etravirine	The serum concentration of Etravirine can be decreased when it is combined with Thiorphan.	Approved
Hexestrol	The serum concentration of Hexestrol can be decreased when it is combined with Thiorphan.	Withdrawn
Imipramine	The serum concentration of Imipramine can be increased when it is combined with Thiorphan.	Approved
Lovastatin	The serum concentration of Lovastatin can be increased when it is combined with Thiorphan.	Approved, Investigational
Mestranol	The serum concentration of Mestranol can be decreased when it is combined with Thiorphan.	Approved
Methallenestril	The serum concentration of Methallenestril can be decreased when it is combined with Thiorphan.	Experimental
Midazolam	The serum concentration of Midazolam can be increased when it is combined with Thiorphan.	Approved, Illicit
Mirtazapine	The serum concentration of Mirtazapine can be increased when it is combined with Thiorphan.	Approved
Nefazodone	The serum concentration of Nefazodone can be increased when it is combined with Thiorphan.	Approved, Withdrawn
Nortriptyline	The serum concentration of Nortriptyline can be increased when it is combined with Thiorphan.	Approved
Opipramol	The serum concentration of Opipramol can be increased when it is combined with Thiorphan.	Investigational
Pethidine	The risk or severity of adverse effects can be increased when Thiorphan is combined with Pethidine.	Approved
Pimozide	The serum concentration of Pimozide can be increased when it is combined with Thiorphan.	Approved
Protriptyline	The serum concentration of Protriptyline can be increased when it is combined with Thiorphan.	Approved
Riociguat	The serum concentration of Riociguat can be increased when it is combined with Thiorphan.	Approved
Rosuvastatin	The serum concentration of Rosuvastatin can be increased when it is combined with Thiorphan.	Approved
Sildenafil	The serum concentration of Sildenafil can be increased when it is combined with Thiorphan.	Approved, Investigational
Simeprevir	The serum concentration of Simeprevir can be increased when it is combined with Thiorphan.	Approved
Simvastatin	The serum concentration of Simvastatin can be increased when it is combined with Thiorphan.	Approved
St. John's Wort	The metabolism of Thiorphan can be increased when combined with St. John's Wort.	Nutraceutical
Synthetic Conjugated Estrogens, A	The serum concentration of Synthetic Conjugated Estrogens, A can be decreased when it is combined with Thiorphan.	Approved
Tacrolimus	The metabolism of Tacrolimus can be decreased when combined with Thiorphan.	Approved, Investigational
Temsirolimus	The risk or severity of adverse effects can be increased when Thiorphan is combined with Temsirolimus.	Approved
Theophylline	The serum concentration of Theophylline can be decreased when it is combined with Thiorphan.	Approved
Tianeptine	The serum concentration of Tianeptine can be increased when it is combined with Thiorphan.	Approved
Tipranavir	The serum concentration of Thiorphan can be decreased when it is combined with Tipranavir.	Approved, Investigational
Triazolam	The serum concentration of Triazolam can be increased when it is combined with Thiorphan.	Approved
Trimipramine	The serum concentration of Trimipramine can be increased when it is combined with Thiorphan.	Approved
Valproic Acid	The serum concentration of Valproic Acid can be decreased when it is combined with Thiorphan.	Approved, Investigational
Verapamil	The metabolism of Verapamil can be decreased when combined with Thiorphan.	Approved
Zidovudine	The serum concentration of Zidovudine can be decreased when it is combined with Thiorphan.	Approved

Food Interactions

Not Available

References

Synthesis Reference

Mohammad R. Masjedizadeh, Shao-Yong Wu, "PROCESS FOR SYNTHESIS OF TRITIATED AND DEUTERATED THIORPHAN AND ACETORPHAN." U.S. Patent US20110319656, issued December 29, 2011.

US20110319656

General References

Not Available

External Links

Resource	Link
KEGG Compound	C01619
PubChem Compound	4369380
PubChem Substance	99445097
ChemSpider	3571959
BindingDB	50024102
ChEMBL	CHEMBL298827
HET	TIO
Wikipedia	Thiorphan

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

1DMT

FDA label

Not Available

MSDS

Not Available

Clinical Trials

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.445 mg/mL	ALOGPS
logP	1.78	ALOGPS
logP	1.46	ChemAxon
logS	-2.8	ALOGPS
pKa (Strongest Acidic)	4.02	ChemAxon
pKa (Strongest Basic)	-1.8	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	66.4 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	67.15 m³·mol^-1	ChemAxon
Polarizability	25.93 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.937
Blood Brain Barrier	+	0.806
Caco-2 permeable	-	0.6428
P-glycoprotein substrate	Non-substrate	0.7192
P-glycoprotein inhibitor I	Non-inhibitor	0.9402
P-glycoprotein inhibitor II	Non-inhibitor	0.9827
Renal organic cation transporter	Non-inhibitor	0.9466
CYP450 2C9 substrate	Non-substrate	0.838
CYP450 2D6 substrate	Non-substrate	0.8369
CYP450 3A4 substrate	Non-substrate	0.8005
CYP450 1A2 substrate	Non-inhibitor	0.9046
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Non-inhibitor	0.923
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.9223
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9729
Ames test	Non AMES toxic	0.5567
Carcinogenicity	Non-carcinogens	0.9183
Biodegradation	Not ready biodegradable	0.5448
Rat acute toxicity	1.6959 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9862
hERG inhibition (predictor II)	Non-inhibitor	0.927

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Taxonomy

Description

This compound belongs to the class of chemical entities known as n-acyl-alpha amino acids. These are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom.

Kingdom

Chemical entities

Super Class

Organic compounds

Class

Organic acids and derivatives

Sub Class

Carboxylic acids and derivatives

Direct Parent

N-acyl-alpha amino acids

Alternative Parents

Fatty amides / Benzene and substituted derivatives / Secondary carboxylic acid amides / Monocarboxylic acids and derivatives / Carboxylic acids / Alkylthiols / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives

Substituents

N-acyl-alpha-amino acid / Monocyclic benzene moiety / Fatty amide / Fatty acyl / Benzenoid / Carboxamide group / Secondary carboxylic acid amide / Alkylthiol / Carboxylic acid / Monocarboxylic acid or derivatives

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

Not Available

Targets

Details

1. Neprilysin

Kind: Protein
Organism: Human
Pharmacological action: unknown
Actions: inhibitor

General Function:: Zinc ion binding
Specific Function:: Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of at...
Gene Name:: MME
Uniprot ID:: P08473
Molecular Weight:: 85513.225 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Drug created on September 15, 2010 15:33 / Updated on June 11, 2017 21:19

Get DrugBank to go!

Structure for DB08626 (Thiorphan)

Targets

References