MERIMEPODIB

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H24N4O6
Molecular Weight	452.4599
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(C=CC(NC(=O)NC2=CC=CC(CNC(=O)O[C@H]3CCOC3)=C2)=C1)C4=CN=CO4

InChI

InChIKey=JBPUGFODGPKTDW-SFHVURJKSA-N

InChI=1S/C23H24N4O6/c1-30-20-10-17(5-6-19(20)21-12-24-14-32-21)27-22(28)26-16-4-2-3-15(9-16)11-25-23(29)33-18-7-8-31-13-18/h2-6,9-10,12,14,18H,7-8,11,13H2,1H3,(H,25,29)(H2,26,27,28)/t18-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11288107
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800008158 http://files.shareholder.com/downloads/VRTX/3251874583x0xS912057-02-12962/875320/filing.pdf https://www.ncbi.nlm.nih.gov/pubmed/23016672

Merimepodib has immunosuppressive activity. It targets hepatitis C indirectly through the inhibition of inositol monophosphate dehydrogenase, which exerts an acute antiproliferative effect on lymphocyte proliferation due to their almost exclusive dependence on the de novo pathway for synthesis of guanosine. Phase II clinical trial study of merimepodib for the treatment of HCV infection and psoriasis were completed. The poor pharmacokinetic-pharmacodynamic results have resulted in discontinuation of clinical trials.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Inosine-5'-monophosphate dehydrogenase 1 4 Target ID: CHEMBL1822 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11288107	Inhibitor 8297
Inosine-5'-monophosphate dehydrogenase 2 4 Target ID: CHEMBL2002 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11288107	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis C 42 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17629590	Primary		Phase II 1132	Unknown Approved Use Unknown
Psoriasis 84 Sources: http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=18910	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1748 ng/mL OTHER https://www.natap.org/1999/aasld/rpt10.htm	100 mg 3 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		MERIMEPODIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3195 ng/mL OTHER https://www.natap.org/1999/aasld/rpt10.htm	200 mg 3 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		MERIMEPODIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3543 ng × h/mL OTHER https://www.natap.org/1999/aasld/rpt10.htm	100 mg 3 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		MERIMEPODIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8210 ng × h/mL OTHER https://www.natap.org/1999/aasld/rpt10.htm	200 mg 3 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		MERIMEPODIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P002C73	https://www.1pchem.com/search?query=1P002C73
AK Scientific	3810AH	https://aksci.com/item_detail.php?cat=3810AH
Ambeed	A470058	http://www.ambeed.com/search/Search.html?keyword=A470058
Angene	AGN-PC-0WHEQO	http://www.angenechemical.com/productshow/AGN-PC-0WHEQO.html
ApexBio Technology	B1112	https://www.apexbt.com/catalogsearch/result/?q=B1112
AstaTech	FD5020	http://astatechinc.com/CPSResult.php?CRNO=FD5020
BLD Pharm	BD447514	http://www.bldpharm.com/search/Search.html?keyword=BD447514
Chem Scene	CS-2105	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-2105
ChemShuttle	169539	https://www.chemshuttle.com/catalogsearch/result/?q=169539
Excenen	EX-A1201	http://www.excenen.com/searchresultlist.php?id=EX-A1201
KeyOrganics	AS-75124	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-75124
MedChem Express	HY-13986	https://www.medchemexpress.com/search.html?q=HY-13986&ft=&fa=&fp=
MolPort	MolPort-006-170-006	https://www.molport.com/shop/molecule-link/MolPort-006-170-006
Molnova	M13108	https://www.molnova.com/en/serch-list.html?keywords=M13108
MuseChem	I002524	https://www.musechem.com/product/I002524.html
ShangHai Biochempartner	BCP28336	http://www.biochempartner.com/search_BCP28336
TargetMol	T3444	https://www.targetmol.com/search?keyword=T3444
Wonderchem	WD09JOH	http://www.wonder-chem.com/search.html?text=WD09JOH
eMolecules	275142280	https://orderbb.emolecules.com/search/#?query=275142280
eMolecules	301064014	https://orderbb.emolecules.com/search/#?query=301064014
eMolecules	49285255	https://orderbb.emolecules.com/search/#?query=49285255
mcule	MCULE-1874571105	https://mcule.com/MCULE-1874571105/
mcule	MCULE-3309832876	https://mcule.com/MCULE-3309832876/

PubMed

Title	Date	PubMed
Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon.	2000 Apr	10722482
Novel approaches to the treatment of hepatitis C virus infection.	2000 Mar	10819433
Discovery of N-[2-[2-[[3-methoxy-4-(5-oxazolyl)phenyl]amino]-5-oxazolyl]phenyl]-N-methyl-4- morpholineacetamide as a novel and potent inhibitor of inosine monophosphate dehydrogenase with excellent in vivo activity.	2002 May 23	12014950
The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA.	2003 Jun 5	12781720

Patents

Sample Use Guides

In Vivo Use Guide

25 or 50 mg every 12h (24 weeks of treatment)

Route of Administration: Oral

In Vitro Use Guide

The IC50 values for VX-497 in Sprague-Dawley or Lewis rat lymphocytes were similar to the 100 nM human PBMC IC50 values.

Name

Type

Language

MERIMEPODIB

Official Name

English

MERIMEPODIB [USAN]

Common Name

English

VX-497

Code

English

CARBAMIC ACID, ((3-((((3-METHOXY-4-(5-OXAZOLYL)PHENYL)AMINO)CARBONYL)AMINO)PHENYL)METHYL)-, (3S)-TETRAHYDRO-3-FURANYL ESTER

Common Name

English

(S)-TETRAHYDRO-3-FURYL (M-(3-(3-METHOXY-4-(5-OXAZOLYL)PHENYL)UREIDO)BENZYL)CARBAMATE

Systematic Name

English

Merimepodib [WHO-DD]

Common Name

English

VI-21,497

Code

English

merimepodib [INN]

Common Name

English

VI-21497

Code

English

MERIMEPODIB [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C281