Home Protein Tyrosine Kinase c-Met inhibitor - FLT3 inhibitor - DDR inhibitor - ROS1 inhibitor - Mertk inhibitor - Axl inhibitor Merestinib (LY2801653)

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Merestinib (LY2801653) c-Met inhibitor

Cat.No.S7014

Merestinib (LY2801653) is a type-II ATP competitive, slow-off inhibitor of Met (c-Met) tyrosine kinase with a dissociation constant (Ki) of 2 nM, a pharmacodynamic residence time (Koff) of 0.00132 min(-1) and t1/2 of 525 min. This compound also inhibits MST1R, AXL, ROS1, MKNK1/2, FLT3, MERTK, DDR1 and DDR2 with IC50 of 11 nM, 2 nM, 23 nM, 7 nM, 7 nM, 10 nM, 0.1 nM and 7 nM, respectively.
Merestinib (LY2801653) c-Met inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 552.53

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Quality Control

Batch: S701401 DMSO]100 mg/mL]false]Ethanol]100 mg/mL]false]Water]Insoluble]false Purity: 99.78%
99.78

Chemical Information, Storage & Stability

Molecular Weight 552.53 Formula

C30H22F2N6O3

 Storage (From the date of receipt)
CAS No. 1206799-15-6 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC1=CC=C(C(=O)N1C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C=C5C(=C4)C=NN5C)C6=CNN=C6)F

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (180.98 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
DDR1 [2]
(Cell-based assay)
0.1 nM
AXL [2]
(Cell-based assay)
2 nM
Met [1]
(Cell-free assay)
2 nM(Ki)
MKNK1/2 [2]
(Cell-based assay)
7 nM
FLT3 [2]
(Cell-based assay)
7 nM
DDR2 [2]
(Cell-based assay)
7 nM
MERTK [2]
(Cell-based assay)
10 nM
MST1R [2]
(Cell-based assay)
11 nM
ROS1 [2]
(Cell-based assay)
23 nM
In vitro

Merestinib (LY2801653) demonstrates in vitro effects on MET pathway-dependent cell scattering and cell proliferation. It demonstrates more potent anti-proliferative activity in cell lines with MET gene amplification (MKN45, Hs746T and H1993) than the cell lines without MET gene amplification (U-87MG, KATO-III). This compound also maintains potency against 13 MET variants, each bearing a single-point mutation. It is found to have potent activity against several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, DDR1/2 and against the serine/threonine kinases MKNK1/2. The mean IC50 value of this chemical for inhibition of MET auto-phosphorylation in HGF-stimulated H460 cells is 35.2±6.9 nM and the IC50 for MET auto-phosphorylation in S114 cells is 59.2 nM[1].
In vivo

Merestinib (LY2801653) shows in vivo anti-tumor effects in MET amplified (MKN45), MET autocrine (U-87MG, and KP4) and MET over-expressed (H441) xenograft models; and in vivo vessel normalization effects. It is able to induce vessel normalization in xenograft tumors. Among the species studied, this compound has the shortest elimination half life in mice of 2.9 h, compared with 14.3 h in non-human primate. It is currently in phase 1 clinical testing in patients with advanced cancer[1].
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03125239 Completed
Relapsed Adult Acute Myeloid Leukemia|Refractory Adult Acute Myeloid Leukemia
Jacqueline Garcia MD|Eli Lilly and Company|Dana-Farber Cancer Institute
 August 10 2017 Phase 1
NCT03027284 Completed
Advanced Cancer|Metastatic Cancer|Biliary Tract Carcinoma|Cholangiocarcinoma|Gall Bladder Carcinoma|Solid Tumor|Non-Hodgkin''s Lymphoma
Eli Lilly and Company
 February 3 2017 Phase 1
NCT02745769 Completed
Advanced Cancer|Colorectal Cancer|Mantle Cell Lymphoma
Eli Lilly and Company
 October 21 2016 Phase 1
NCT02779738 Completed
Healthy
Eli Lilly and Company
 May 2016 Phase 1

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