Merestinib dihydrochloride

SKU: orb1707040

Description

Merestinib dihydrochloride is an orally bioavailable small molecule inhibitor targeting kinases including MET, AXL, RON, and MKNK1/2. It demonstrates antitumor activity in preclinical studies, showing efficacy against tumors harboring NTRK fusions in both cellular assays and in vivo models.

Research Area

Cardiovascular Research, Signal Transduction

Images & Validation

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Key Properties

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CAS Number	1206801-37-7
MW	625.45
Formula	C₃₀H₂₄Cl₂F₂N₆O₃
SMILES	Cc1ccc(C(=O)Nc2ccc(Oc3cc4cnn(C)c4cc3-c3cn[nH]c3)c(F)c2)c(=O)n1-c1ccc(F)cc1.Cl.Cl
Target	Tyrosine Kinases,Discoidin Domain Receptor (DDR),c-Met/HGFR,ROS Kinase,TAM Receptor,FLT
Solubility	DMSO:80 mg/mL (127.91 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (5.28 mM)

Bioactivity

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Target IC50	Axl:2 nM\|c-Met:2 nM (Ki)\|MKNK1/2:7 nM\|DDR1/2:0.1-7 nM\|TEK:63 nM\|MerTK:10 nM\|FLT3:7 nM\|HGF-stimulated H460 cells:35.2 nM\|S114 cells:59.2 nM\|MST1R:11 nM
In Vivo	Merestinib dihydrochloride showed significant antitumor effects in a MET-amplified xenograft model (MKN45), a MET autocrine model (U-87MG and KP4), and a MET overexpression model (H441), as well as in vivo vasculature normalization. As a type II ATP-competitive inhibitor, Merestinib dihydrochloride is a slow dissociating inhibitor of MET tyrosine kinase with a pharmacodynamic residence time (Koff) of 0.00132 min^-1 and a half-life (t1/2) of 525 min.Merestinib dihydrochloride treatment inhibited MET phosphorylation with a combined TED50 (50% targeted inhibitor dose) of 1.2 mg/kg and TED90 (90% targeted inhibitor dose) of 7.4 mg/kg.With Merestinib dihydrochloride (20 mg/kg), TFK-1 tumor growth was significantly lower than that of the control group. In addition, Merestinib dihydrochloride effectively inhibited the growth of intrahepatic and extrahepatic cholangiocarcinoma (CCC) xenograft tumors. Read more...
In Vitro	Merestinib dihydrochloride is a potent, orally bioavailable c-Met inhibitor with a Ki value of 2 nM and significant antitumor activity. In addition, Merestinib dihydrochloride showed significant antitumor activity against MST1R (IC50=11 nM), FLT3 (IC50=7 nM), AXL (IC50=2 nM), MERTK (IC50=10 nM), TEK (IC50=63 nM), ROS1, DDR1/2 (IC50=0.1/7 nM) and MKNK1/2 (IC50=7 nM) showed potent activity. Merestinib dihydrochloride affected MET pathway-dependent cell scattering and proliferation. In HGF-stimulated H460 cells, the mean IC50 value for Merestinib dihydrochloride on MET autophosphorylation was 35.2 nM, compared to 59.2 nM in S114 cells. Transfection of MET variants gave cells growth factor independence, and treatment with Merestinib dihydrochloride was able to inhibit the growth of these MET variant clones with IC50 values ranging from approximately 3-fold more potent (V1092I) to approximately 6-fold less potent (L1195V) compared to MET wild-type sequences. Read more...

Storage & Handling

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Storage	keep away from moisture,store at low temperature \| Powder: -20°C for 3 years \| In solvent: -80°C for 1 year \| Shipping with blue ice/Shipping at ambient temperature.
Expiration Date	12 months from date of receipt.
Disclaimer	For research use only

Alternative Names

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TEK, TAM Receptor, TAMReceptor, Tyrosine Kinases, TyrosineKinases, MKNK1/2, LY 2801653, LY 2801653 dihydrochloride, LY2801653, LY-2801653 Dihydrochloride, LY-2801653, LY2801653 dihydrochloride, MST1R, FLT3, DDR1/2, HGFR, MERTK, Merestinib, AXL, cMet/HGFR, c-Met, cMet

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Compound Identifiers

PubChem CID

71604306 ↗

Key Properties

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No computed properties available.

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