olmutinib   

GtoPdb Ligand ID: 9196

Synonyms: BI-1482694 | Example 1 [US20130116213] | HM-61713 | HM61713
olmutinib is an approved drug (South Korea (2016))
Compound class: Synthetic organic
Comment: Olmutinib from Hanmi Pharmaceutical, approved in South Korea for lung cancer, targets mutant epidermal growth factor receptor (EGFR) selectively over wild-type. It is reported as an oral, third-generation EGFR tyrosine kinase inhibitor (binding covalently), however there is no published, peer-reviewed data to confirm this. The potential for using third-generation EGFR inhibitors in EGFR-mutated non-small lung cancer is reviewed by Russo et al. (2017) [7]. Olmutinib is claimed in patent WO2011162515 [1]. Full text descriptions and structure images are available in US20130116213 [3], where it is identified as Example 1 (N-(3-(2-(4-(4-methylpiperazin-1-yl)phenylamino)thieno[3,2-d]pyrimidin-4-yloxy)phenyl)acrylamide). Note we updated this entry in Nov 2016 with the removal of the incorrect synonyms HM-71224 and LY3337641 which refer to a blinded Hanmi BTK inhibitor [4].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 110.86
Molecular weight 486.18
XLogP 4.26
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES C=CC(=O)Nc1cccc(c1)Oc1nc(Nc2ccc(cc2)N2CCN(CC2)C)nc2c1scc2
Isomeric SMILES C=CC(=O)Nc1cccc(c1)Oc1nc(Nc2ccc(cc2)N2CCN(CC2)C)nc2c1scc2
InChI InChI=1S/C26H26N6O2S/c1-3-23(33)27-19-5-4-6-21(17-19)34-25-24-22(11-16-35-24)29-26(30-25)28-18-7-9-20(10-8-18)32-14-12-31(2)13-15-32/h3-11,16-17H,1,12-15H2,2H3,(H,27,33)(H,28,29,30)
InChI Key FDMQDKQUTRLUBU-UHFFFAOYSA-N
Bioactivity Comments
No technical papers have yet appeared (Nov 2016) but the Hanmi patent [1] includes binned IC50 data for 150 analogues. Olmutinib is recorded as having <50nM for inhibition of EGFR with L858R/T790M mutation, two other mutations and 100-1000nM for wild type EGFR . In these biochemical assays olmutinib was more selective for the mutant EGFR than erlotinib. Inhibition data for cancer cell lines is also provided, with GI50 values of <50nM vs. cells with DelE746_A750 or L858R/T790M EGFR mutations, and >1000nM for cells with wild type EGFR.
Selectivity at catalytic receptors
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
epidermal growth factor receptor Hs Inhibitor Inhibition 6.0 – 7.0 pIC50 - 1
pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [1]
Description: Biochemical assay