MERESTINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H22F2N6O3
Molecular Weight	552.5309
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1N=CC2=C1C=C(C3=CNN=C3)C(OC4=C(F)C=C(NC(=O)C5=CC=C(C)N(C5=O)C6=CC=C(F)C=C6)C=C4)=C2

InChI

InChIKey=QHADVLVFMKEIIP-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.lillyoncologypipeline.com/molecule/met-inhibitor/overview | https://www.ncbi.nlm.nih.gov/pubmed/23275061
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27307295 https://www.ncbi.nlm.nih.gov/pubmed/23989980

Merestinib (LY2801653) is a small molecule that has been shown in vitro to be a reversible type II ATP-competitive slowoff inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM, a pharmacodynamic residence time (Koff) of 0.00132 min−1 and a half-life (t1/2) of 525 min. Preclinical testing also has shown merestinib to inhibit several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, NTRK1/2/3, and DDR1/2 and the serine/threonine kinases MKNK1/2. Merestinib is being investigated in a phase II clinical trials in patients with biliary tract cancer, non-small cell lung cancer and solid tumours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23275061	Inhibitor 8297		2.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Biliary tract cancer 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02711553 http://adisinsight.springer.com/drugs/800033685	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://clinicaltrials.gov/ct2/show/NCT02920996	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT02920996	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678278	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363678278	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363678278	yes [IC50 2.6837 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678278	yes [IC50 4.6109 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY103044	https://www.001chemical.com/chem/search?q=DY103044
1PlusChem LLC	1P003B3B	https://www.1pchem.com/search?query=1P003B3B
1PlusChem LLC	1P008TY9	https://www.1pchem.com/search?query=1P008TY9
AK Scientific	3797AH	https://aksci.com/item_detail.php?cat=3797AH
AK Scientific	SYN1222	https://aksci.com/item_detail.php?cat=SYN1222
Ambeed	A221593	http://www.ambeed.com/search/Search.html?keyword=A221593
Angene	AGN-PC-0WADMM	http://www.angenechemical.com/productshow/AGN-PC-0WADMM.html
ApexBio Technology	A3573	https://www.apexbt.com/catalogsearch/result/?q=A3573
Axon MedChem	2553	https://www.axonmedchem.com/product/2553
BLD Pharm	BD280343	http://www.bldpharm.com/search/Search.html?keyword=BD280343
BLD Pharm	BD629992	http://www.bldpharm.com/search/Search.html?keyword=BD629992
Chem Scene	CS-1192	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1192
Chem Scene	CS-1438	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1438
ChemShuttle	101176	https://www.chemshuttle.com/catalogsearch/result/?q=101176
Excenen	EX-A1264	http://www.excenen.com/searchresultlist.php?id=EX-A1264
KeyOrganics	AS-16348	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16348
Matrix Scientific	120708	http://www.matrixscientific.com/120708.html
MedChem Express	HY-15514	https://www.medchemexpress.com/search.html?q=HY-15514A&ft=&fa=&fp=
MedChem Express	HY-15514A	https://www.medchemexpress.com/search.html?q=HY-15514A&ft=&fa=&fp=
MolPort	MolPort-028-720-434	https://www.molport.com/shop/molecule-link/MolPort-028-720-434
MolPort	MolPort-046-417-061	https://www.molport.com/shop/molecule-link/MolPort-046-417-061
Molcore	MC103044	http://www.molcore.com/CatMC103044.html
MuseChem	I007960	https://www.musechem.com/product/I007960.html
Selleck Chemicals	S7014	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7014
ShangHai Biochempartner	BCP000736	http://www.biochempartner.com/search_BCP000736
ShangHai Biochempartner	BCP06826	http://www.biochempartner.com/search_BCP06826
ShangHai Biochempartner	BCP13049	http://www.biochempartner.com/search_BCP13049
eMolecules	44827783	https://orderbb.emolecules.com/search/#?query=44827783
eMolecules	49837432	https://orderbb.emolecules.com/search/#?query=49837432
mcule	MCULE-1457543573	https://mcule.com/MCULE-1457543573/
mcule	MCULE-9847198344	https://mcule.com/MCULE-9847198344/

PubMed

Title	Date	PubMed
Inhibition of tumor growth and metastasis in non-small cell lung cancer by LY2801653, an inhibitor of several oncokinases, including MET.	2013 Oct 15	23989980
Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo.	2016 Jul 21	27307295

Patents

Sample Use Guides

In Vivo Use Guide

Merestinib at the recommended phase II dose of 120 mg by mouth daily.

Route of Administration: Oral

In Vitro Use Guide

Merestinib, in the concentration range of 0.01–10 uM, completely blocked the HGF-induced DU-145 cell scattering.

Name

Type

Language

MERESTINIB

Official Name

English

3-PYRIDINECARBOXAMIDE, N-(3-FLUORO-4-((1-METHYL-6-(1H-PYRAZOL-4-YL)-1H-INDAZOL-5-YL)OXY)PHENYL)-1-(4-FLUOROPHENYL)-1,2-DIHYDRO-6-METHYL-2-OXO-

Systematic Name

English

LY-2801653

Code

English

MERESTINIB [USAN]

Common Name

English

merestinib [INN]

Common Name

English

LY2801653

Code

English

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

Systematic Name

English

Merestinib [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825