LY2801653 | Merestinib | CAS#1206799-15-6 | 1206801-37-7 | c-Met inhibitor

MedKoo Cat#: 205526 | Name: Merestinib (LY2801653)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Merestinib is a potent, orally bioavailable, multi-kinase inhibitor primarily targeting MET (c-Met), with reported IC₅₀ values in the low nanomolar range (e.g., ~2–3 nM for MET). It also inhibits a range of receptor tyrosine kinases including AXL, RON, ROS1, NTRK1/2/3, FLT3, and DDR1/2. In preclinical studies, Merestinib demonstrated strong anti-proliferative effects in MET-amplified and MET-mutant cancer cell lines, with dose-dependent inhibition of MET phosphorylation and downstream signaling pathways (e.g., ERK and AKT). In xenograft models, Merestinib suppressed tumor growth in MET-driven tumors. It has also shown activity against NTRK fusion-positive cancers, leading to tumor regression in relevant models

Chemical Structure

Merestinib (LY2801653)

CAS#1206799-15-6 (free base)

Theoretical Analysis

MedKoo Cat#: 205526

Name: Merestinib (LY2801653)

CAS#: 1206799-15-6 (free base)

Chemical Formula: C30H22F2N6O3

Exact Mass: 552.1722

Molecular Weight: 552.53

Elemental Analysis: C, 65.21; H, 4.01; F, 6.88; N, 15.21; O, 8.69

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 300.00	Ready to ship
50mg	USD 500.00	Ready to ship
100mg	USD 850.00	Ready to ship
200mg	USD 1,450.00	Ready to ship
500mg	USD 2,950.00	Ready to ship

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Related CAS #

1206799-15-6 (free base) 1206801-37-7 (HCl)

Synonym

LY-2801653; LY 2801653; LY2801653; Merestinib;

IUPAC/Chemical Name

N-(3-fluoro-4-((1-methyl-6-(1H-pyrazol-4-yl)-1H-indazol-5-yl)oxy)phenyl)-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide

InChi Key

QHADVLVFMKEIIP-UHFFFAOYSA-N

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)

SMILES Code

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

Appearance

White to off-white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

LY2801653 was identified and developed as a novel, potent, and orally active small molecule inhibitor of human c-Met. It demonstrated dose dependent inhibition of c-Met phosphorylation in xenograft tumors with a long lasting PD effect. LY2801653 displayed potent anti-tumor efficacy in a number of non small cell lung, renal, pancreatic, and breast tumor models. Examination of c-Met expression in these tumors by immunohistochemistry (IHC) revealed a good correlation between response and c-Met expression in the tumor tissue. LY2801653 treatment led to increase in functional vessel areas, and decrease in tumor hypoxia. Enhanced anti-tumor efficacy was achieved when Erlotinib was combined with LY2801653. . (source: http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/70/8_MeetingAbstracts/3611). (source: http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/70/8_MeetingAbstracts/3611).

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB60328

QC Data

View QC data: current batch, Lot#CRB60328

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Merestinib (LY2801653) is a potent, c-Met inhibitor (Ki=2 nM) with anti-tumor activities and 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.

In vitro activity:

To examine if merestinib inhibits NTRK1 phosphorylation in vitro, KM-12 cells were treated for 2 hours ranging in concentration from 3.9 -1000 nM. Merestinib showed a dose dependent decrease in p-NTRK1 Y490 resulting in complete inhibition at 62.5 nM as determined by western blot (Figure1B). Merestinib showed dose dependent inhibition of phosphorylated MAPK 42/44 (ERK) in concordance with their respective p-NTRK downstream signaling (Figure1B). Merestinib is a potent direct inhibitor of MKNK1/2, the kinases responsible for phosphorylating eIF4E at S209 [16]. In KM-12 cells, merestinib reduced p-eIF4E levels with near-complete inhibition at 62.5 nM (Figure1B). It was further examined if merestinib, M1 and M2 metabolites suppress KM-12 cell proliferation in vitro. Within 72 hours, treatment with merestinib, M1, or M2 suppressed cell proliferation with an IC50 of 10 nM, 16 nM and 102 nM, respectively. Collectively, these data suggest that merestinib and the metabolites M1 and M2 block both anchorage dependent and independent cell growth in TPM3-NTRK1 bearing KM-12 cells. Reference: Oncotarget. 2018 Mar 2; 9(17): 13796–13806. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862616/

In vivo activity:

Merestinib (dosed once daily at 12 mg/kg or 24 mg/kg) (dosed twice daily at 30 mg/kg) was evaluated in mouse tumor models with NIH-3T3 cells expressing wild-type TPM3-NTRK1, TPM3-NTRK1 with G595R or G667C mutation. Merestinib treatment resulted in tumor regression in tumors expressing wild-type TPM3-NTRK1 (Figure6A). Similar extent of tumor regression was observed in both doses of merestinib treated cohorts in animals bearing tumors with the G667C mutant within 4 days of treatment initiation (12 mg/kg once daily, regression = 46.8%, p < 0.001; 24 mg/kg once daily, regression = 51.3%, p < 0.001) and maintained through the study period. Tumors expressing mutant G595R TPM3-NTRK1 insensitive to merestinib (T/C=65.2%, p=0.147) treatment (Figure (Figure 6C). Together, these data indicate that merestinib is a potent inhibitor of NTRK and blocks tumor progression in vivo in preclinical studies. Reference: Oncotarget. 2018 Mar 2; 9(17): 13796–13806. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862616/

	Solvent	mg/mL	mM
Solubility
	DMSO	66.0	119.45

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 552.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Konicek BW, Capen AR, Credille KM, Ebert PJ, Falcon BL, Heady GL, Patel BKR, Peek VL, Stephens JR, Stewart JA, Stout SL, Timm DE, Um SL, Willard MD, Wulur IH, Zeng Y, Wang Y, Walgren RA, Betty Yan SC. Merestinib (LY2801653) inhibits neurotrophic receptor kinase (NTRK) and suppresses growth of NTRK fusion bearing tumors. Oncotarget. 2018 Feb 13;9(17):1379613806. doi: 10.18632/oncotarget.24488. PMID: 29568395; PMCID: PMC5862616. 2. Kosciuczuk EM, Saleiro D, Kroczynska B, Beauchamp EM, Eckerdt F, Blyth GT, Abedin SM, Giles FJ, Altman JK, Platanias LC. Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo. Blood. 2016 Jul 21;128(3):410-4. doi: 10.1182/blood-2016-02-698704. Epub 2016 Jun 15. PMID: 27307295; PMCID: PMC4957163.

In vitro protocol:

In vivo protocol:

1: Luo X, Linghu M, Zhou X, Ru Y, Huang Q, Liu D, Ji S, Ma Y, Luo Y, Huang Y. Merestinib inhibits cuproptosis by targeting NRF2 to alleviate acute liver injury. Free Radic Biol Med. 2025 Mar 1;229:68-81. doi: 10.1016/j.freeradbiomed.2025.01.029. Epub 2025 Jan 15. PMID: 39824447. 2: Thawani R, Repetto M, Keddy C, Nicholson K, Jones K, Nusser K, Beach CZ, Harada G, Drilon A, Davare MA. TKI type switching overcomes ROS1 L2086F in ROS1 fusion-positive cancers. NPJ Precis Oncol. 2024 Aug 8;8(1):175. doi: 10.1038/s41698-024-00663-1. Erratum in: NPJ Precis Oncol. 2024 Aug 28;8(1):184. doi: 10.1038/s41698-024-00676-w. PMID: 39117775; PMCID: PMC11310217. 3: Devi GR, Pai P, Lee S, Foster MW, Sannareddy DS, Bertucci F, Ueno N, Van Laere S. Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer. NPJ Breast Cancer. 2024 Jul 29;10(1):65. doi: 10.1038/s41523-024-00664-0. PMID: 39075068; PMCID: PMC11286775. 4: Thawani R, Repetto M, Keddy C, Nicholson K, Jones K, Nusser K, Beach CZ, Harada G, Drilon A, Davare MA. TKI Type Switching Overcomes ROS1 L2086F in ROS1 Fusion-Positive Cancers. bioRxiv [Preprint]. 2024 Jan 19:2024.01.16.575901. doi: 10.1101/2024.01.16.575901. Update in: NPJ Precis Oncol. 2024 Aug 8;8(1):175. doi: 10.1038/s41698-024-00663-1. PMID: 38293020; PMCID: PMC10827145. 5: Wang ML, Jurczak W, Zinzani PL, Eyre TA, Cheah CY, Ujjani CS, Koh Y, Izutsu K, Gerson JN, Flinn I, Tessoulin B, Alencar AJ, Ma S, Lewis D, Lech-Maranda E, Rhodes J, Patel K, Maddocks K, Lamanna N, Wang Y, Tam CS, Munir T, Nagai H, Hernandez-Ilizaliturri F, Kumar A, Fenske TS, Seymour JF, Zelenetz AD, Nair B, Tsai DE, Balbas M, Walgren RA, Abada P, Wang C, Zhao J, Mato AR, Shah NN. Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle- Cell Lymphoma. J Clin Oncol. 2023 Aug 20;41(24):3988-3997. doi: 10.1200/JCO.23.00562. Epub 2023 May 16. PMID: 37192437; PMCID: PMC10461952. 6: Chen EC, Gandler H, Tošić I, Fell GG, Fiore A, Pozdnyakova O, DeAngelo DJ, Galinsky I, Luskin MR, Wadleigh M, Winer ES, Leonard R, O'Day K, de Jonge A, Neuberg D, Look AT, Stone RM, Frank DA, Garcia JS. Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates. Clin Cancer Res. 2023 Mar 1;29(5):878-887. doi: 10.1158/1078-0432.CCR-22-2540. PMID: 36534523; PMCID: PMC9992000. 7: Feng L, Wang Y, Xu H, Yi F. Comparison of Different First-Line Systemic Therapies in Advanced Biliary Tract Cancer Based on Updated Random Controlled Trials: A Systematic Review and Network Meta-Analysis. Biomed Res Int. 2022 Sep 9;2022:1720696. doi: 10.1155/2022/1720696. PMID: 36119936; PMCID: PMC9481325. 8: Fujino T, Suda K, Koga T, Hamada A, Ohara S, Chiba M, Shimoji M, Takemoto T, Soh J, Mitsudomi T. Foretinib can overcome common on-target resistance mutations after capmatinib/tepotinib treatment in NSCLCs with MET exon 14 skipping mutation. J Hematol Oncol. 2022 Jun 11;15(1):79. doi: 10.1186/s13045-022-01299-z. PMID: 35690785; PMCID: PMC9188708. 9: Bahcall M, Paweletz CP, Kuang Y, Taus LJ, Sim T, Kim ND, Dholakia KH, Lau CJ, Gokhale PC, Chopade PR, Hong F, Wei Z, Köhler J, Kirschmeier PT, Guo J, Guo S, Wang S, Jänne PA. Combination of Type I and Type II MET Tyrosine Kinase Inhibitors as Therapeutic Approach to Prevent Resistance. Mol Cancer Ther. 2022 Feb;21(2):322-335. doi: 10.1158/1535-7163.MCT-21-0344. Epub 2021 Nov 17. PMID: 34789563; PMCID: PMC8828669. 10: Valle JW, Vogel A, Denlinger CS, He AR, Bai LY, Orlova R, Van Cutsem E, Adeva J, Chen LT, Obermannova R, Ettrich TJ, Chen JS, Wasan H, Girvan AC, Zhang W, Liu J, Tang C, Ebert PJ, Aggarwal A, McNeely SC, Moser BA, Oliveira JM, Carlesi R, Walgren RA, Oh DY. Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, multicentre, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1468-1482. doi: 10.1016/S1470-2045(21)00409-5. Erratum in: Lancet Oncol. 2021 Nov;22(11):e472. doi: 10.1016/S1470-2045(21)00586-6. PMID: 34592180. 11: Doi T, Yamamoto N, Naito Y, Kuboki Y, Koyama T, Piao Y, Tsujimoto N, Asou H, Inoue K, Kondo S. Merestinib monotherapy or in combination for japanese patients with advanced and/or metastatic cancer: A phase 1 study. Cancer Med. 2021 Oct;10(19):6579-6589. doi: 10.1002/cam4.4110. Epub 2021 Sep 9. PMID: 34499416; PMCID: PMC8495281. 12: Zhang S, Stroud PA, Zhu A, Johnson MJ, Lomeo J, Burcham CL, Hinds J, Allen- Francis Blakely K, Walworth MJ. Characterizing the Impact of Spray Dried Particle Morphology on Tablet Dissolution Using Quantitative X-Ray Microscopy. Eur J Pharm Sci. 2021 Oct 1;165:105921. doi: 10.1016/j.ejps.2021.105921. Epub 2021 Jul 3. PMID: 34229077. 13: Patnaik A, Yap TA, Chung HC, de Miguel MJ, Bang YJ, Lin CC, Su WC, Italiano A, Chow KH, Szpurka AM, Yu D, Zhao Y, Carlsen M, Schmidt S, Vangerow B, Gandhi L, Xu X, Bendell J. Safety and Clinical Activity of a New Anti-PD-L1 Antibody as Monotherapy or Combined with Targeted Therapy in Advanced Solid Tumors: The PACT Phase Ia/Ib Trial. Clin Cancer Res. 2021 Mar 1;27(5):1267-1277. doi: 10.1158/1078-0432.CCR-20-2821. Epub 2020 Nov 23. PMID: 33229456. 14: Saleh M, Cassier PA, Eberst L, Naik G, Morris VK, Pant S, Terret C, Gao L, Long A, Mao H, McNeely S, Wagner EK, Carlesi RM, Fu S. Phase I Study of Ramucirumab Plus Merestinib in Previously Treated Metastatic Colorectal Cancer: Safety, Preliminary Efficacy, and Pharmacokinetic Findings. Oncologist. 2020 Nov;25(11):e1628-e1639. doi: 10.1634/theoncologist.2020-0520. Epub 2020 Jul 17. PMID: 32537847; PMCID: PMC7648328. 15: Huang C, Zou Q, Liu H, Qiu B, Li Q, Lin Y, Liang Y. Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations. Curr Treat Options Oncol. 2020 Apr 18;21(4):33. doi: 10.1007/s11864-020-0723-5. PMID: 32306194. 16: Chu P, Batson S, Hodgson M, Mitchell CR, Steenrod A. Systematic review of neurotrophic tropomyosin-related kinase inhibition as a tumor-agnostic management strategy. Future Oncol. 2020 Feb;16(4):61-74. doi: 10.2217/fon-2019-0534. Epub 2020 Jan 16. PMID: 31942815. 17: He AR, Cohen RB, Denlinger CS, Sama A, Birnbaum A, Hwang J, Sato T, Lewis N, Mynderse M, Niland M, Giles J, Wallin J, Moser B, Zhang W, Walgren R, Plimack ER. First-in-Human Phase I Study of Merestinib, an Oral Multikinase Inhibitor, in Patients with Advanced Cancer. Oncologist. 2019 Sep;24(9):e930-e942. doi: 10.1634/theoncologist.2018-0411. Epub 2019 Mar 4. PMID: 30833489; PMCID: PMC6738318. 18: Ghanaatgar-Kasbi S, Khorrami S, Avan A, Aledavoud SA, Ferns GA. Targeting the C-MET/HGF Signaling Pathway in Pancreatic Ductal Adenocarcinoma. Curr Pharm Des. 2018;24(39):4619-4625. doi: 10.2174/1381612825666190110145855. PMID: 30636579. 19: Konicek BW, Capen AR, Credille KM, Ebert PJ, Falcon BL, Heady GL, Patel BKR, Peek VL, Stephens JR, Stewart JA, Stout SL, Timm DE, Um SL, Willard MD, Wulur IH, Zeng Y, Wang Y, Walgren RA, Betty Yan SC. Merestinib (LY2801653) inhibits neurotrophic receptor kinase (NTRK) and suppresses growth of NTRK fusion bearing tumors. Oncotarget. 2018 Feb 13;9(17):13796-13806. doi: 10.18632/oncotarget.24488. PMID: 29568395; PMCID: PMC5862616. 20: Yan SB, Um SL, Peek VL, Stephens JR, Zeng W, Konicek BW, Liu L, Manro JR, Wacheck V, Walgren RA. MET-targeting antibody (emibetuzumab) and kinase inhibitor (merestinib) as single agent or in combination in a cancer model bearing MET exon 14 skipping. Invest New Drugs. 2018 Aug;36(4):536-544. doi: 10.1007/s10637-017-0545-x. Epub 2017 Nov 29. PMID: 29188469; PMCID: PMC6061111.