GtoPdb Ligand ID: 9667

Synonyms: compound 40 [PMID: 28498658] | PF06650833
Compound class: Synthetic organic
Comment: PF-06650833 is a small molecule, reversible, potent and selective IRAK4 inhibitor identified as a clinical lead [1]. Its pharmacokinetic profile suggests it will be orally bioavailable. Structurally it is an analogue of PF-06426779.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 103.54
Molecular weight 361.14
XLogP 2
No. Lipinski's rules broken 0
Canonical SMILES CCC1C(COc2nccc3c2cc(OC)c(c3)C(=O)N)NC(=O)C1F
Isomeric SMILES CC[C@H]1[C@@H](COc2nccc3c2cc(OC)c(c3)C(=O)N)NC(=O)[C@H]1F
InChI InChI=1S/C18H20FN3O4/c1-3-10-13(22-17(24)15(10)19)8-26-18-11-7-14(25-2)12(16(20)23)6-9(11)4-5-21-18/h4-7,10,13,15H,3,8H2,1-2H3,(H2,20,23)(H,22,24)/t10-,13+,15-/m0/s1
Immunopharmacology Comments
IRAK4 is a key node in innate immune signaling that is activated by interleukin (IL)‑1 family receptors and Toll-like receptors. Blocking IRAK4 suppresses the immune response to Toll ligands and IL-1 and blocks production of inflammatory cytokines (type I interferons, IL‑6, TNF, IL‑1, and IL‑12). This mechanism is predicted to be effective against cytokine driven autoimmune diseases, with minimal immunosuppressive side effects, and is being investigated for potential to treat autoimmune diseases and sterile inflammation. PF-06650833 is a Phase 2 lead for RA, and has shown preclinical potential in models of SLE and IBD.
Immunopharmacology Disease
Disease X-Refs Comment References
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
Phase 2 clinical candidate for RA- see NCT02996500. 1