PLX5622   Click here for help

GtoPdb Ligand ID: 9105

Synonyms: PLX 5622 | PLX-5622
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: PLX5622 is an orally available and highly selective kinase inhibitor targeting CSF1R (FMS) kinase and other Type III receptor tyrosine kinases. It is being investigated for its anti-inflammatory effects in autoimmune diseases, in the first instance rheumatoid arthritis (RA).
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 70.37
Molecular weight 395.41
XLogP 0.87
No. Lipinski's rules broken 0
Click here for help
Canonical SMILES CC1=CC2=C(N=C1)NC=C2CC3=CC=C(NCC4=C(N=CC(=C4)F)OC)N=C3F
Isomeric SMILES CC1=CC2=C(NC=C2CC3=C(N=C(C=C3)NCC4=C(N=CC(=C4)F)OC)F)N=C1
InChI InChI=1S/C21H19F2N5O/c1-12-5-17-14(9-26-20(17)25-8-12)6-13-3-4-18(28-19(13)23)24-10-15-7-16(22)11-27-21(15)29-2/h3-5,7-9,11H,6,10H2,1-2H3,(H,24,28)(H,25,26)
No information available.
Summary of Clinical Use Click here for help
A Phase 1b study of PLX5622 in RA patients receiving methotrexate therapy has been completed- see NCT01329991.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
An increasing number of diseases are now recognized as being driven by inflammatory processes, and consequently involve various cells of the immune system. These cells include macrophages, microglial cells, T-cells, B-cells, monocytes and mast cells. CSF1R inhibitors are expected to target pro-inflammatory macrophages in inflamed joints of RA patients as well as reducing bone erosion and pain through inhibition of osteoclasts.
Alzheimer's disease (neuroinflammation): PLX5622 has been shown to eliminate microglia from the brain, which can be sustained in wild-type and the Alzheimer's disease model mice (3xTg-AD model). In the AD model PLX5622 prevents microglial association with amyloid β plaques and improves cognition [1].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01329991 Phase 1b Study of PLX5622 in Rheumatoid Arthritis Patients Who Are Receiving Methotrexate Phase 1 Interventional Plexxikon