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| 25mg |
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Purity: ≥98%
Merestinib (LY-2801653) is a novel, potent, orally bioavailable, type-II ATP competitive, slow-off small molecule inhibitor of 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. According to an in vitro study, c-MET kinase activity was shown to be inhibited as 0.01–10 μM LY2801653, which was able to totally block HGF-induced DU–145 cell scattering. LY2801653 exhibited more potent anti-proliferative activity against cell lines expressing the MET gene than against cell lines lacking the gene expression, according to the results of a panel of cell lines screening for the drug.
| Targets |
c-Met (Ki = 2 nM); MST1R (IC50 = 11 nM); FLT3 (IC50 = 7 nM); AXL (IC50 = 2 nM); MERTK (IC50 = 10 nM); TEK (IC50 = 63 nM); DDR1/2 (IC50 = 0.1/7 nM); MKNK1/2 (IC50 = 7 nM)
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| ln Vitro |
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| Enzyme Assay |
LY2801653, a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase, has a pharmacodynamic residence time (K(off)) of 0.00132 min(-1) and a dissociation constant (K(i)) of 2 nM. Its t(1/2) is 525 minutes.
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| Cell Assay |
H460 cells are cultivated in RPMI media supplemented with 10% FBS, plated at 20,000 cells/well in 96-well plates before they reach 70% confluency, and then incubated at 37°C for the entire night. Before being treated with Merestinib (LY2801653), the cells are cultured with RPMI-1640 in low serum (0.5% FBS) for two hours on the following day. HGF is added thirty minutes after Merestinib (LY2801653), with a final concentration of 100ng/mL. The next step involves preparing cell lysates and quantifying pMET following a 10-minute incubation. With regard to on-plate MIN (unstimulated) and MAX controls, the percentage of inhibition is calculated to obtain the relative IC50 values. The percentage-of-inhibition values and the 10-point dose response data are then fitted to a 4-parameter logistic equation using ActivityBase[1].
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| Animal Protocol |
Mice: Subcutaneous implants of S114 cells are made in female athymic nude mice. On day 8 following implantation, a range of 0.75 mg/kg to 100 mg/kg of merestinib is administered (n = 8 per dose group) for the purpose of evaluating the dose response. Blood samples and tumors are taken and flash frozen two hours after the dose. Merestinib is administered at a dose of 12 mg/kg (n=10 per time point) in the time course study. Blood samples and tumor samples are taken after the animals are sacrificed 2, 8, 16, and 24 hours after the dose. The MSD ELISA assay is used to quantify pMET in the S114 tumor lysates. Pulverized frozen tumor tissue is used to create lysates, which are then homogenized using Lysing Matrix D beads and RIPA lysis buffer that contains protease and phosphatase inhibitors. The DC protein assay kit is used to measure protein concentration. It is done using the pMET MSD ELISA assay.
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| References |
| Molecular Formula |
C30H22F2N6O3
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| Molecular Weight |
552.53
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| Exact Mass |
552.17
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| Elemental Analysis |
C, 65.21; H, 4.01; F, 6.88; N, 15.21; O, 8.69
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| CAS # |
1206799-15-6
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| Related CAS # |
Merestinib dihydrochloride;1206801-37-7
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| Appearance |
White to off-white solid powder
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| 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
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| InChi Key |
QHADVLVFMKEIIP-UHFFFAOYSA-N
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| InChi Code |
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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| Chemical Name |
N-[3-fluoro-4-[1-methyl-6-(1H-pyrazol-4-yl)indazol-5-yl]oxyphenyl]-1-(4-fluorophenyl)-6-methyl-2-oxopyridine-3-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.76 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02920996 | Active Recruiting |
Drug: Merestinib | Carcinoma, Non-Small-Cell Lung Solid Tumor |
Dana-Farber Cancer Institute | November 11, 2016 | Phase 2 |
| NCT02711553 | Active Recruiting |
Drug: Merestinib Drug: Cisplatin |
Biliary Tract Cancer Metastatic Cancer |
Eli Lilly and Company | May 19, 2016 | Phase 2 |
| NCT03125239 | Completed | Drug: Merestinib Drug: LY2874455 |
Relapsed Adult Acute Myeloid Leukemia Refractory Adult Acute Myeloid Leukemia |
Jacqueline Garcia, MD | August 10, 2017 | Phase 1 |
| NCT03027284 | Completed | Drug: Merestinib Drug: Cisplatin |
Advanced Cancer Solid Tumor |
Eli Lilly and Company | February 3, 2017 | Phase 1 |
| NCT02779738 | Completed | Drug: Merestinib | Healthy | Eli Lilly and Company | May 2016 | Phase 1 |
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