[CAS NO. 1206799-15-6] Merestinib

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PRODUCTS SPECIFICATIONS [1206799-15-6]

Catalog

HY-15514

Brand

MCE

CAS

1206799-15-6

DESCRIPTION [1206799-15-6]

Overview

MDL	MFCD23160048
Molecular Weight	552.53
Molecular Formula	C30H22F2N6O3
SMILES	O=C(C1=CC=C(C)N(C2=CC=C(F)C=C2)C1=O)NC3=CC=C(OC4=CC5=C(N(C)N=C5)C=C4C6=CNN=C6)C(F)=C3

For research use only. We do not sell to patients.

4 Publications Citing Use of MCE

Summary

Merestinib (LY2801653) is a potent, orally bioavailable c-Met inhibitor ( K _i =2 nM) with anti-tumor activities. Merestinib (LY2801653) also has potent activity against MST1R (IC ₅₀ =11 nM), FLT3 (IC ₅₀ =7 nM), AXL (IC ₅₀ =2 nM), MERTK (IC ₅₀ =10 nM), TEK (IC ₅₀ =63 nM), ROS1, DDR1/2 (IC ₅₀ =0.1/7 nM) and MKNK1/2 (IC ₅₀ =7 nM) ^[1] ^[2] .

IC50 & Target

Ki: 2 nM (c-Met) ^[1]
IC50: 11 nM (MST1R), 7 nM (FLT3), 2 nM (AXL), 10 nM (MERTK), 63 nM (TEK), 0.1/7 nM (DDR1/2), 7 nM (MKNK1/2) ^[1]

In Vitro

Merestinib (LY2801653) demonstrates effects on MET pathway-dependent cell scattering and cell proliferation. The mean IC ₅₀ value (n=6 determinations) of Merestinib (LY2801653) for inhibition of MET auto-phosphorylation in HGF-stimulated H460 cells is 35.2±6.9 nM and the IC ₅₀ for MET auto-phosphorylation in S114 cells is 59.2 nM. Merestinib (LY2801653) also inhibits MST1R (IC ₅₀ =11 nM), AXL (IC ₅₀ =2 nM), MERTK (IC ₅₀ =10 nM), TYRO3 (IC50=28 nM), ROS1, PDGFRA (IC50=41 nM), FLT3 (IC ₅₀ =7 nM), TEK (IC50=63 nM), DDR1/2 (IC ₅₀ =0.1/7 nM) and MKNK1/2 (IC ₅₀ =7 nM) ^[1] .
Transfection with the MET variants confers growth-factor independence and treatment with Merestinib (LY2801653) inhibits growth of these MET variant clones with an IC ₅₀ ranging from 3-fold more potent (V1092I) to approximately 6-fold less potent (L1195V) compare with the growth inhibition of cells with the MET wild-type sequence ^[1] . Merestinib (LY2801653) (2, 5, and 10 μM) reduces the number of viable TFK-1 and SZ-1 cells in a dose and time dependent manner, and significant inhibits wound healing for TFK-1 and SZ-1 cell lines. Merestinib (LY2801653) inhibits cell invasion in TFK-1 and SZ-1 cells in a concentration dependent manner ^[2] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Merestinib (LY2801653) demonstrates 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. Merestinib (LY2801653) is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a pharmacodynamic residence time (K _off ) of 0.00132 min ^-1 and t _1/2 of 525 min. Merestinib (LY2801653) treatment inhibits MET phosphorylation with a composite TED50 (50 % target inhibition dose) of 1.2 mg/kg and a composite TED90 (90 % target inhibition dose) of 7.4 mg/kg ^[1] . Merestinib (LY2801653) (20 mg/kg) reduces TFK-1 tumor growth significantly relative to vehicle control. Merestinib (LY2801653) inhibits the growth of intra- and extrahepatic CCC xenograft tumors ^[2] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT03125239	Jacqueline Garcia, MD\|Eli Lilly and Company\|Dana-Farber Cancer Institute	Relapsed Adult Acute Myeloid Leukemia\|Refractory Adult Acute Myeloid Leukemia	August 10, 2017	Phase 1
NCT01285037	Eli Lilly and Company	Cancer	September 9, 2009	Phase 1
NCT02370485	Eli Lilly and Company	Healthy	February 2015	Phase 1
NCT02745769	Eli Lilly and Company	Advanced Cancer\|Colorectal Cancer\|Mantle Cell Lymphoma	October 21, 2016	Phase 1
NCT03027284	Eli Lilly and Company	Advanced Cancer\|Metastatic Cancer\|Biliary Tract Carcinoma\|Cholangiocarcinoma\|Gall Bladder Carcinoma\|Solid Tumor\|Non-Hodgkin´s Lymphoma	February 3, 2017	Phase 1
NCT02920996	Dana-Farber Cancer Institute\|Eli Lilly and Company	Carcinoma, Non-Small-Cell Lung\|Solid Tumor	November 11, 2016	Phase 2
NCT02779738	Eli Lilly and Company	Healthy	May 2016	Phase 1
NCT02791334	Eli Lilly and Company	Solid Tumor\|Microsatellite Instability-High (MSI-H) Solid Tumors\|Cutaneous Melanoma\|Pancreatic Cancer\|Breast Cancer (HR&addition;HER2-)	June 29, 2016	Phase 1
NCT02711553	Eli Lilly and Company	Biliary Tract Cancer\|Metastatic Cancer\|Advanced Cancer	May 19, 2016	Phase 2
NCT03292536	University of Utah\|Eli Lilly and Company	Bone Metastases\|Breast Cancer	January 11, 2018	Phase 1

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : ≥ 32 mg/mL ( 57.92 mM )

* "≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.8099 mL	9.0493 mL	18.0986 mL
5 mM	0.3620 mL	1.8099 mL	3.6197 mL
10 mM	0.1810 mL	0.9049 mL	1.8099 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 2.08 mg/mL (3.76 mM); Clear solution
2.

Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.08 mg/mL (3.76 mM); Clear solution
3.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 2.08 mg/mL (3.76 mM); Clear solution

* All of the co-solvents are available by MCE.