merestinib   Click here for help

GtoPdb Ligand ID: 9841

Synonyms: LY-2801653 | LY2801653
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Merestinib (LY2801653) is a type II ATP-competitive multikinase inhibitor [4]. It inhibits several kinases including the oncokinases MET (the hepatocyte growth factor [HGF] receptor), RON (MST1R), AXL, MERTK, MKNK1/2, and Tie2/TEK. Merestinib exhibits anti-tumour activity in vitro and in vivo and is orally available.
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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 7
Topological polar surface area 106.31
Molecular weight 552.17
XLogP 6.5
No. Lipinski's rules broken 1
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Canonical SMILES Fc1ccc(cc1)n1c(C)ccc(c1=O)C(=O)Nc1ccc(c(c1)F)Oc1cc2cnn(c2cc1c1c[nH]nc1)C
Isomeric SMILES Fc1ccc(cc1)n1c(C)ccc(c1=O)C(=O)Nc1ccc(c(c1)F)Oc1cc2cnn(c2cc1c1c[nH]nc1)C
InChI InChI=1S/C30H22F2N6O3/c1-17-3-9-23(30(40)38(17)22-7-4-20(31)5-8-22)29(39)36-21-6-10-27(25(32)12-21)41-28-11-18-16-35-37(2)26(18)13-24(28)19-14-33-34-15-19/h3-16H,1-2H3,(H,33,34)(H,36,39)
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Summary of Clinical Use Click here for help
Merestinib (LY2801653) has reached Phase 2 clinical development as a potential therapeutuc to treat various solid tumours. It is being evaluated as a single agent in Phase 2 clinical trial NCT02920996 (for NSCLC with MET transformation or other advanced solid tumours with NTRK1, 2, or 3 rearrangements), and in combination with other oncotherapeutics in separate trials.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
The proto-oncogene c-Met is overexpressed or mutated in many tumours where its dysregulated signalling plays key roles in cellular proliferation, survival, invasion, metastasis, and angiogenesis of the developing tumour. Merestinib binds to c-Met and inhibits its signalling capacity.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02920996 Merestinib In Non-Small Cell Lung Cancer And Solid Tumors Phase 2 Interventional Dana-Farber Cancer Institute