AVOSENTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H21N5O5S
Molecular Weight	479.508
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=CC=C1OC2=C(NS(=O)(=O)C3=CC=C(C)C=N3)N=C(N=C2OC)C4=CC=NC=C4

InChI

InChIKey=YBWLTKFZAOSWSM-UHFFFAOYSA-N

InChI=1S/C23H21N5O5S/c1-15-8-9-19(25-14-15)34(29,30)28-22-20(33-18-7-5-4-6-17(18)31-2)23(32-3)27-21(26-22)16-10-12-24-13-11-16/h4-14H,1-3H3,(H,26,27,28)

HIDE SMILES / InChI

Molecular Formula	C23H21N5O5S
Molecular Weight	479.508
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16740981 | https://www.ncbi.nlm.nih.gov/pubmed/23228194

Avosentan is an oral endothelin receptor A antagonist which was developed by Roche and then licensed by Speedel (now Novartis). The drug was tested in phase III of clinical trials in patients suffering from diabetic nephropathy, however drug development was terminated due to safety reasons: avosentan caused severe heart failure and even deaths.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Endothelin receptor ET-A 19 Target ID: CHEMBL252 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22529820	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetic nephropathy 35 Sources: https://clinicaltrials.gov/ct2/show/NCT00120328	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
19.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	0.5 mg 1 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1883.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
228.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
54.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	1.5 mg 1 times / day multiple, oral dose: 1.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
247 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	0.5 mg 1 times / day multiple, oral dose: 0.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
15646 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	50 mg 1 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2106 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	5 mg 1 times / day multiple, oral dose: 5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
641 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19279566	1.5 mg 1 times / day multiple, oral dose: 1.5 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AVOSENTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A 191

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A 191	substrate 3367 Sources: https://clinicaltrials.gov/ProvidedDocs/68/NCT01923168/Prot_001.pdf	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY115076	https://www.001chemical.com/chem/search?q=DY115076
1PlusChem LLC	1P002XPI	https://www.1pchem.com/search?query=1P002XPI
ApexBio Technology	A3208	https://www.apexbt.com/catalogsearch/result/?q=A3208
BOC Sciences	290815-26-8	http://www.bocsci.com/description.asp?cas=290815-26-8
Chem Scene	CS-0625	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0625
Hairui	HR113220	http://www.hairuichem.com/en/product/search.do?q=HR113220
Matrix Scientific	98678	http://www.matrixscientific.com/098678.html
MedChem Express	HY-15195	https://www.medchemexpress.com/search.html?q=HY-15195&ft=&fa=&fp=
MolPort	MolPort-027-835-678	https://www.molport.com/shop/molecule-link/MolPort-027-835-678
Molcore	MC115076	http://www.molcore.com/CatMC115076.html
MuseChem	I003008	https://www.musechem.com/product/I003008.html
MuseChem	R055773	https://www.musechem.com/product/R055773.html
Toronto Research Chemicals	A794710	https://www.trc-canada.com/product-detail/?CatNum=A794710
eMolecules	43548339	https://orderbb.emolecules.com/search/#?query=43548339
mcule	MCULE-9377409317	https://mcule.com/MCULE-9377409317/

PubMed

Title	Date	PubMed
Influence of avosentan (SPP3OI) on the pharmacokinetics of a second generation oral contraceptive containing ethinylestradiol and levonorgestrel in healthy female volunteers.	2006 Dec	17190377
Profile of past and current clinical trials involving endothelin receptor antagonists: the novel "-sentan" class of drug.	2006 Jun	16740981
Influence of food intake on the pharmacokinetics of avosentan in man.	2008 Sep	18793575
Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist avosentan in healthy subjects.	2009 Jun	19279566
Avosentan reduces albumin excretion in diabetics with macroalbuminuria.	2009 Mar	19144760
Unlike each drug alone, lisinopril if combined with avosentan promotes regression of renal lesions in experimental diabetes.	2009 Nov	19675181
Absolute bioavailability and pharmacokinetics of avosentan in man.	2009 Sep	19761718
Channels and transporters. Mini-symposium of the Division of Medicinal Chemistry (DMC) of the Swiss Chemical Society (SCS) at the Department of Chemistry, University of Basel, May 27, 2010.	2010	21138110
Antiatherosclerotic and renoprotective effects of ebselen in the diabetic apolipoprotein E/GPx1-double knockout mouse.	2010 Dec	20823099
The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice.	2010 Jan	19862499
Avosentan for overt diabetic nephropathy.	2010 Mar	20167702

Patents

Sample Use Guides

In Vivo Use Guide

Oral avosentan is administered once daily at doses of 25 or 50 mg.

Route of Administration: Oral

In Vitro Use Guide

Porcine ciliary arteries were incubated with avosentan (10(-6) M and 10(-8) M) and then exposed, cumulatively, to increasing concentrations of endothelin-1 (10(-12) M-3 × 10(-8) M). Avosentan had a strong inhibitory effect on the endothelin-1-induced contractions. The inhibitory effect of 10(-6) M avosentan was significantly stronger than the effect of 10(-8) M avosentan.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:19:53 UTC 2023` Edited by `admin` on `Fri Dec 15 17:19:53 UTC 2023`
Record UNII	L94KSX715K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AVOSENTAN

Official Name

English

RO 67-0565

Code

English

avosentan [INN]

Common Name

English

2-PYRIDINESULFONAMIDE, N-(6-METHOXY-5-(2-METHOXYPHENOXY)-2-(4-PYRIDINYL)-4-PYRIMIDINYL)-5-METHYL-

Systematic Name

English

RO-67-0565

Code

English

N-(6-METHOXY-5-(2-METHOXYPHENOXY)-2-(PYRIDIN-4-YL)PYRIMIDIN-4-YL)-5-METHYLPYRIDINE-2-SULFONAMIDE

Systematic Name

English

SPP-301

Code

English

Code System Code Type Description

PUBCHEM

9912992