NEFLAMAPIMOD

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H9Cl2F2N3OS
Molecular Weight	436.262
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=C(SC2=NN3C=NC(=O)C(=C3C=C2)C4=C(Cl)C=CC=C4Cl)C(F)=C1

InChI

InChIKey=VEPKQEUBKLEPRA-UHFFFAOYSA-N

InChI=1S/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H

HIDE SMILES / InChI

Molecular Formula	C19H9Cl2F2N3OS
Molecular Weight	436.262
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/24900264 | http://www.prnewswire.com/news-releases/eip-pharma-announces-positive-results-with-neflamapimod-vx-745-in-two-phase-2a-clinical-trials-in-patients-with-early-alzheimers-disease-300375145.html | https://www.ncbi.nlm.nih.gov/pubmed/11892915

VX-745 (Neflamapimod) is a brain-penetrant highly selective, orally bioavailable drug that inhibits the intracellular enzyme p38 mitogen-activated protein kinase alpha (MAPKa). It is currently in phase 2 clinical studies in patients with early Alzheimer's disease. The targeting of p38 MAPK by VX-745 was associated with the suppression of the release of inflammatory mediators, including interleukin (IL)-1β and tumor necrosis factor (TNF)α, known to be implicated in exacerbating the pathophysiology of rheumatoid arthritis (RA). The drug was in phase II of the clinical trial for RA, but that studies were discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenosine transporter 1 1 Target ID: CHEMBL2601 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900264	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alzheimer’s disease 272 Sources: http://www.prnewswire.com/news-releases/eip-pharma-announces-positive-results-with-neflamapimod-vx-745-in-two-phase-2a-clinical-trials-in-patients-with-early-alzheimers-disease-300375145.html	Primary		Phase II 1132	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11892915	Primary		Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781	inhibitor 1767 inducer 389	inducer 97 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2A6 707 CYP2E1 882 BSEP 402 CYP2C19 1478 CYP1A2 1524		CYP1A2 701 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity
CYP2A6 739	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExOTM4NSJ9fQ==	no [IC50 >10 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDExOTM4NSJ9fQ==	no [IC50 >10 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no [IC50 >40 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no [IC50 >40 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no [IC50 >40 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no [IC50 >40 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no [IC50 >40 uM]
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no
CYP2C19 1553	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no
CYP2C9 1819	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no
CYP2D6 1891	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/	no
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22961681/	yes [IC50 <10 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY113464	https://www.001chemical.com/chem/search?q=DY113464
1PlusChem LLC	1P002KOM	https://www.1pchem.com/search?query=1P002KOM
AK Scientific	SYN1123	https://aksci.com/item_detail.php?cat=SYN1123
AK Scientific	W4385	https://aksci.com/item_detail.php?cat=W4385
AOBIOUS INC	AOB6867	http://aobious.com/aobious/search?search_query=AOB6867
Ambeed	A189058	http://www.ambeed.com/search/Search.html?keyword=A189058
Angene	AGN-PC-0QWSRS	http://www.angenechemical.com/productshow/AGN-PC-0QWSRS.html
ApexBio Technology	A8686	https://www.apexbt.com/catalogsearch/result/?q=A8686
AstaTech	42308	http://astatechinc.com/CPSResult.php?CRNO=42308
Axon MedChem	1811	https://www.axonmedchem.com/product/1811
BOC Sciences	209410-46-8	http://www.bocsci.com/description.asp?cas=209410-46-8
Capot Chemical	17468	https://www.capotchem.com/search.do?q=17468
Cayman Chemical	18075	http://www.caymanchem.com/app/template/Product.vm/catalog/18075
Chem Scene	CS-0195	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0195
ChemShuttle	101973	https://www.chemshuttle.com/catalogsearch/result/?q=101973
Combi-Blocks	QJ-0680	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-0680
Debye Scientific	DB-000564	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-000564
Excenen	EX-A854	http://www.excenen.com/searchresultlist.php?id=EX-A854
Fluorochem	92709	http://www.fluorochem.co.uk/Products/Product?code=092709
Hairui	HR102653	http://www.hairuichem.com/en/product/search.do?q=HR102653
KeyOrganics	5T-0205	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=5T-0205
Lab Seeker	SC-82791	http://www.labseeker.com/search.php?keywords=SC-82791&category=0
LabSeeker	SC-82791	http://www.labseeker.com/search.php?keywords=SC-82791&category=0
Matrix Scientific	90324	http://www.matrixscientific.com/090324.html
MedChem Express	HY-10328	https://www.medchemexpress.com/search.html?q=HY-10328&ft=&fa=&fp=
MolPort	MolPort-005-942-914	https://www.molport.com/shop/molecule-link/MolPort-005-942-914
Molcore	MC113464	http://www.molcore.com/CatMC113464.html
Molnova	M13290	https://www.molnova.com/en/serch-list.html?keywords=M13290
MuseChem	I002609	https://www.musechem.com/product/I002609.html
PI Chemicals	PI-33971	http://www.pipharm.com/catalog_products/PI-33971.html
ShangHai Biochempartner	BCP000138	http://www.biochempartner.com/search_BCP000138
ShangHai Biochempartner	BCP01837	http://www.biochempartner.com/search_BCP01837
TargetMol	T6089	https://www.targetmol.com/search?keyword=T6089
Tetrahedron	TS33179	http://www.thsci.com/search.do?q=TS33179
Tocris	3915	https://www.tocris.com/search.php?Type=QuickSearch&Value=3915
Toronto Research Chemicals	F594100	https://www.trc-canada.com/product-detail/?CatNum=F594100
Toronto Research Chemicals	V900500	https://www.trc-canada.com/product-detail/?CatNum=V900500
eMolecules	32176610	https://orderbb.emolecules.com/search/#?query=32176610
eNovation Chemicals	D372529	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372529&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-2083764937	https://mcule.com/MCULE-2083764937/

PubMed

Title	Date	PubMed
		252160473
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378

Sample Use Guides

In Vivo Use Guide

VX-745 dose level 1 twice daily

Route of Administration: Oral

In Vitro Use Guide

Cell data for VX-745 in a human peripheral blood mononuclear cell (PBMC) assay provided IC50 values of 56 and 52 nM for IL-1β and TNFα, respectively, and VX-745 blocked IL-6 and IL-8 production induced by IL-1 and TNFα, and cyclooxygenase (COX)-2 synthesis mediated by LPS and IL-1β. In a human whole blood assay, IC50 values were 152 and 177 nM for IL-1β and TNFα inhibition, respectively.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:58:51 GMT 2023` Edited by `admin` on `Fri Dec 15 15:58:51 GMT 2023`
Record UNII	TYL52QM320
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NEFLAMAPIMOD

Official Name

English

neflamapimod [INN]

Common Name

English

NEFLAMAPIMOD [USAN]

Common Name

English

6H-PYRIMIDO(1,6-B)PYRIDAZIN-6-ONE, 5-(2,6-DICHLOROPHENYL)-2-((2,4-DIFLUOROPHENYL)THIO)-

Systematic Name

English

VX-745

Code

English

VRT-031745

Code

English

Neflamapimod [WHO-DD]

Common Name

English

VD-31,745

Code

English

VD-31745

Code

English

5-(2,6-DICHLOROPHENYL)-2-((2,4-DIFLUOROPHENYL)THIO)-6H-PYRIMIDO(1,6-B)PYRIDAZINE-6-ONE

Systematic Name

English

Code System Code Type Description

SMS_ID

100000183677