(R)-STU104   Click here for help

GtoPdb Ligand ID: 12006

Synonyms: (R)-4e [PMID: 35442672]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: (R)-STU104 is a first-in-class molecule that inhibits the interaction between the proteins kinases TAK1 (mitogen-activated protein kinase kinase kinase 7; MAP3K7) and MKK3 (mitogen-activated protein kinase kinase 3; MAP2K3) [1]. These kinases are part of the inflammatory signalling cascade that culminates in TNF-α production. (R)-STU104 binds to MKK3 at a location that disrupts its interaction with the upstream kinase TAK1. This action perturbs MKK3 phosphorylation by TAK1 and inhibits downstream signal propagation. Blocking TAK1-mediated phosphorylation of MKK3 with (R)-STU104 reduces TNF-α in vitro and in mouse models of chronic ulcerative colitis (UC). In the mouse models (R)-STU104 was a more effective UC treatment than the approved UC drug mesalazine (a PPARγ inhibitor). In addition to TNF-α, (R)-STU104 reduced production of several pro-inflammatory cytokines in vivo, including IL-1β, IL-6, and IL-23.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 1
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 44.76
Molecular weight 298.12
XLogP 2.81
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES COc1ccc(cc1)[C@H]1CC(=O)c2c1c(OC)cc(c2)OC
Isomeric SMILES O=C1C[C@H](c2ccc(OC)cc2)c2c(OC)cc(OC)cc12
InChI InChI=1S/C18H18O4/c1-20-12-6-4-11(5-7-12)14-10-16(19)15-8-13(21-2)9-17(22-3)18(14)15/h4-9,14H,10H2,1-3H3/t14-/m1/s1
InChI Key OYJBHGSSAJNKJF-CQSZACIVSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
(3R)-4,6-dimethoxy-3-(4-methoxyphenyl)-2,3-dihydroinden-1-one
Synonyms Click here for help
(R)-4e [PMID: 35442672]
Database Links Click here for help
GtoPdb PubChem SID 464244147
PubChem CID 156579934
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UniChem Connectivity Search for chemical match using the InChIKey OYJBHGSSAJNKJF-CQSZACIVSA-N