Details of the Drug

General Information of Drug (ID: DMJAEG6)

Drug Name
VX-745
Synonyms
5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6H-pyrimido[1,6-b]pyridazin-6-one; 209410-46-8; Neflamapimod; VX 745; VX745; VRT-031745; UNII-TYL52QM320; TYL52QM320; CHEBI:90528; 5-(2,6-dichlorophenyl)-2-(2,4-difluorophenylthio)-6H-pyrimido[1,6-b]pyridazin-6-one; 5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one; Neflamapimod (USAN); Neflamapimod [USAN]; AK-44905; C19H9Cl2F2N3OS; 5-(2,6-Dichlorophenyl)-2-[(2,4-Difluorophenyl)sulfanyl]-6h-Pyrimido[1,6-B]pyridazin-6-One; VX745, VX-745; 5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6H-pyrimido(1,6-b)pyridazin-6-one; Vertex 745 (VX745)
Indication
Disease Entry ICD 11 Status REF
Alzheimer disease 8A20 Phase 2 [1]
Rheumatoid arthritis FA20 Phase 2 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 436.3
Logarithm of the Partition Coefficient (xlogp) 5.1
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C19H9Cl2F2N3OS
IUPAC Name
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one
Canonical SMILES
C1=CC(=C(C(=C1)Cl)C2=C3C=CC(=NN3C=NC2=O)SC4=C(C=C(C=C4)F)F)Cl
InChI
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
InChIKey
VEPKQEUBKLEPRA-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
3038525
ChEBI ID
CHEMBL119385
CAS Number
209410-46-8
UNII
TYL52QM320
DrugBank ID
DB07138
TTD ID
D02NNV
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
MAP kinase p38 (MAPK12) TTYT93M MK12_HUMAN Inhibitor [3]
Stress-activated protein kinase 2a (p38 alpha) TTQBR95 MK14_HUMAN Inhibitor [4]
Stress-activated protein kinase 2b (p38 beta) TT73U6C MK11_HUMAN Inhibitor [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Vascular endothelial growth factor A, long form OTIM9MZ3 VEGFA_HUMAN Protein Interaction/Cellular Processes [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Alzheimer disease
ICD Disease Classification 8A20
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Stress-activated protein kinase 2a (p38 alpha) DTT MAPK14 4.95E-14 0.48 1.09
Stress-activated protein kinase 2b (p38 beta) DTT MAPK11 3.40E-03 -0.12 -0.29
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5719).
3 P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond). 2008 Dec 4;5:22.
4 Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
5 Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. Blood. 2003 Jan 15;101(2):703-5. doi: 10.1182/blood-2002-06-1874. Epub 2002 Sep 5.