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
No information available.
Summary of Clinical Use
Olmutinib has been approved in South Korea (May 2016) [2] for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC), who had been previously treated with an EGFR tyrosine kinase inhibitor (based on results from trial NCT01588145 [6]). Additional Phase 2 clinical trials in T790M-positive non-small cell lung cancer are ongoing- see NCT02485652 [5] and NCT02444819 for example. Olmutinib has been granted breakthrough therapy designation in NSCLC by the US FDA (December 2015). In Sept 2016 Boehringer Ingelheim announced that olmutinib develpment would be returned to Hanmi but it's unclear if this will affect US approval.
Mechanism Of Action and Pharmacodynamic Effects
Olmutinib inhibits T790M mutant EGFR and EGFR activating mutants whilst sparing wild-type receptor activity, thereby showing selectivity towards cancer cells harbouring these receptor tyrosine kinase mutations.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01588145 Phase I/II Trial to Evaluate Safety, Tolerability and Pharmacokinetic Profile of HM61713 in NSCLC Patients Phase 1/Phase 2 Interventional Hanmi Pharmaceutical Company Limited
NCT02444819 Phase II Trial to Evaluate the Efficacy and Safety of HM61713 as the 1st-line NSCLC Anticancer Therapy Phase 2 Interventional Hanmi Pharmaceutical Company Limited
NCT02485652 Phase II Trial of HM61713 for the Treatment of ≥2nd Line T790M Mutation Positive Adenocarcinoma of the Lung Phase 2 Interventional Hanmi Pharmaceutical Company Limited