M4205   Click here for help

GtoPdb Ligand ID: 11510

Synonyms: compound 32 [PMID: 36728508] | IDRX-42 [1] | IDRX42 | M-4205
PDB Ligand
Compound class: Synthetic organic
Comment: M4205 is a potent and selective inhibitor of the KIT proto-oncogene, receptor tyrosine kinase (cKIT). It retains activity against cKIT with exon 11, 13 or 17 resistance mutations, and provides good selectivity in biochemical and cellular assays. M4205's ADME profile supports its potential as an orally bioavailable clinical candidate [1].
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 1
Rotatable bonds 10
Topological polar surface area 85.4
Molecular weight 508.27
XLogP 4.58
No. Lipinski's rules broken 0
Click here for help
Canonical SMILES Cn1ncc(c1)c1ccc(cc1)CNc1ncnc(c1)c1cnc2n1ccc(c2)OCCCN1CCCC1
Isomeric SMILES Cn1ncc(c1)c1ccc(cc1)CNc1ncnc(c1)c1cnc2n1ccc(c2)OCCCN1CCCC1
InChI InChI=1S/C29H32N8O/c1-35-20-24(18-34-35)23-7-5-22(6-8-23)17-30-28-16-26(32-21-33-28)27-19-31-29-15-25(9-13-37(27)29)38-14-4-12-36-10-2-3-11-36/h5-9,13,15-16,18-21H,2-4,10-12,14,17H2,1H3,(H,30,32,33)
Bioactivity Comments
M4205 inhibits cKITV654A with IC50 10 nM, and it achieves 65% inhibition of wild type cKIT activity in vitro. It is not a very selective inhibitor, as it has nanomolar potency (in a biochemical screening assay) at all of the Type III receptor tyrosine kinases [1]. In this assay system, M4205 exhibited slightly improved selectivity in comparison to the approved KIT inhibitors sunitinib, regorafenib, and ripretinib.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
platelet derived growth factor receptor beta Hs Inhibitor Inhibition 8.6 pIC50 - 1
pIC50 8.6 (IC50 2.6x10-9 M) [1]
Description: Biochemical inhibitory potency
colony stimulating factor 1 receptor Hs Inhibitor Inhibition 8.3 pIC50 - 1
pIC50 8.3 (IC50 5.5x10-9 M) [1]
Description: Biochemical inhibitory potency
KIT proto-oncogene, receptor tyrosine kinase Hs Inhibitor Inhibition 7.4 pIC50 - 1
pIC50 7.4 (IC50 4.4x10-8 M) [1]
platelet derived growth factor receptor alpha Hs Inhibitor Inhibition 7.3 pIC50 - 1
pIC50 7.3 (IC50 5x10-8 M) [1]
Description: Biochemical inhibitory potency