Merestinib (LY2801653)

Catalog No.S7014 Batch:S701401

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Technical Data

Formula

C30H22F2N6O3
Molecular Weight 552.53 CAS No. 1206799-15-6
Solubility (25°C)* In vitro DMSO 100 mg/mL (180.98 mM)
Ethanol 100 mg/mL (180.98 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5% DMSO 95% Corn oil
0.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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. Merestinib (LY2801653) 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.
Targets
DDR1 [2]
(Cell-based assay)		 AXL [2]
(Cell-based assay)		 Met [1]
(Cell-free assay)		 MKNK1/2 [2]
(Cell-based assay)		 FLT3 [2]
(Cell-based assay)		 View More
0.1 nM 2 nM 2 nM(Ki) 7 nM 7 nM
In vitro

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). LY2801653 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 LY2801653 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

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, LY2801653 has the shortest elimination half life in mice of 2.9 h, compared with 14.3 h in non-human primate. LY2801653 is currently in phase 1 clinical testing in patients with advanced cancer[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    DU145 cells

  • Concentrations

    0.01-10 μM

  • Incubation Time

    48 h

  • Method

    2×103 DU145 cells/well on poly-D-lysine 96-well black/clear plates are treated with LY2801653 (in 0.4 % DMSO), immediately followed by the addition of human HGF (20 ng/ml), and incubated for 48 h at 37 °C. 2 % formaldehyde fixed cells are stained with AlexaFluor 488 Phalloidin and counterstained with Propidium Iodide. Colony counts are quantified on Acumen Explorer™ laser-scanning fluorescence microplate cytometer. A colony is defined as≥4 cells.
Animal Study:

[1]
  • Animal Models

    Athymic nude mice and CD-1 nude mice

  • Dosages

    0.75 mg/kg to 100 mg/kg

  • Administration

    oral administration

Selleck's Merestinib (LY2801653) has been cited by 10 publications

Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer [ NPJ Breast Cancer, 2024, 10(1):65] PubMed: 39075068
Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition [ Cancers (Basel), 2024, 16(12)2253] PubMed: 38927958
Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts [ J Clin Invest, 2021, 131(11)146987] PubMed: 33905375
Combination of type I and type II MET tyrosine kinase inhibitors as therapeutic approach to prevent resistance [ Mol Cancer Ther, 2021, molcanther.0344.2021] PubMed: 34789563
The STAT3 inhibitor Stattic acts independently of STAT3 to decrease histone acetylation and modulate gene expression [ J Biol Chem, 2021, 296:100220] PubMed: 33839684
Modulating the Function of ABCB1: In Vitro and in Vivo Characterization of Sitravatinib, a Tyrosine Kinase Inhibitor [ Cancer Commun (Lond), 2020, 11] PubMed: 32525624
Sitravatinib, a Tyrosine Kinase Inhibitor, Inhibits the Transport Function of ABCG2 and Restores Sensitivity to Chemotherapy-Resistant Cancer Cells in vitro [ Front Oncol, 2020, 12;10:700] PubMed: 32477943
Sensitivity and Resistance of MET Exon 14 Mutations in Lung Cancer to Eight MET Tyrosine Kinase Inhibitors In Vitro. [ J Thorac Oncol, 2019, 14(10):1753-1765] PubMed: 31279006
[ Oncoimmunology, 2018, ] PubMed: 30228950
Acquired resistance to AZD9291 as an upfront treatment is dependent on ERK signaling in a preclinical model [Ku BM PLoS One, 2018, 13(4):e0194730] PubMed: 29641535

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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