zimlovisertib   Click here for help

GtoPdb Ligand ID: 9667

Synonyms: compound 40 [PMID: 28498658] | PF-06650833 | PF06650833
PDB Ligand Immunopharmacology Ligand
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. The chemical structure for the INN zimlovisertib is identical to the structure of PF-06650833.
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2D Structure
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Physico-chemical Properties
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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
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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
Bioactivity Comments
PF-06650833 inhibits TLR7/8 agonist R848-induced TNFα production in human peripheral blood mononuclear cells with an IC50 of 2nM [1]. Further preclinical results detailing the pharmacokinetic and ADME profiles of PF-06650833 are reported in [1]. In a kinome selectivity profile 200nM PF-06650833 completely inhibited IRAK4 activity, and inhibited the additional kinases IRAK1, MNK2, LRRK2, CLK4, and CK1γ1 by > 70%. In a more physiologically relevant screen, other than IRAK4, 200nM PF-06650833 inhibited only CK1γ2, IRAK3/M, PIPK2C, and CK1δ/ε by > 50%.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
interleukin 1 receptor associated kinase 4 Primary target of this compound Hs Inhibitor Inhibition 9.7 pIC50 - 1
pIC50 9.7 (IC50 2x10-10 M) [1]