Name: Tepotinib (EMD-1214063)
Brand: Selleck Chemicals
SKU: S7067
Rating: 5 (24 reviews)

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Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.58%

99.58

Relaterade mål	EGFR VEGFR FGFR PDGFR Src MEK CSF-1R HER2 FLT3 c-Kit
Övrigt c-Met Inhibitorer	Dihexa SGX-523 PHA-665752 Foretinib (GSK1363089, XL880) SU11274 BMS-777607 JNJ-38877605 Tivantinib PF-04217903 Savolitinib (AZD6094)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer	Analystyp	Koncentration	Inkubationstid	Aktivitetsbeskrivning	PMID
A549	Function assay		45 mins	Inhibition of c-Met kinase in human A549 cells assessed as inhibition of phosphorylation after 45 mins by electrochemiluminescence assay, IC50=0.012μM	25736998
EBC1	Antitumor assay	15 mg/kg	5 days	Antitumor activity against human EBC1 cells xenografted in CD-1 nude mouse assessed as tumor regression at 15 mg/kg, po qd administered for 5 days on and 2 days off up to 32 days	25736998
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt	492.57	Formel	C₂₉H₂₈N₆O₂	Lagring (från mottagningsdatumet)	3 år-20°Cpulver
CAS-nr	1100598-32-0	Ladda ner SDF		Lagring av stamlösningar	1 år-80°Ci lösningsmedel 1 månad-20°Ci lösningsmedel
Synonymer	EMD 1214063, MSC2156119			Smiles	CN1CCC(CC1)COC2=CN=C(N=C2)C3=CC=CC(=C3)CN4C(=O)C=CC(=N4)C5=CC=CC(=C5)C#N

Löslighet (Solubility)

In vitro
Batch:

DMSO : 17 mg/mL (34.51 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Ethanol : 6 mg/mL

Water : Insoluble

Molaritetsräknare

Massa	Koncentration	Volym	Molekylvikt
=	×	×

Utspädningsräknare Molekylviktsräknare

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	2.000mg/ml (4.06mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 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.

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

Dosering: mg/kg Djurens medelvikt: g Doseringsvolym per djur:μL Antal djur:

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH₂O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC₅₀/Ki	c-Met (Cell-free assay) 4 nM
In vitro	EMD 1214063 inhibits HGF-induced c-Met phosphorylation in A549 cells with IC50 of 6 nM. Treatment with this compound induces a marked reduction of c-Met–constitutive phosphorylation in EBC-1 cells with IC50 of 9 nM. It effectively blocka phosphorylation of the major downstream effectors of the c-Met enzyme, such as Grb2, Gab1, Sos, PLCγ, and phosphoinositide 3-kinase, in EBC-1, MKN-45, and Hs746T cells in the range of 1 to 10 nM. This chemical considerably inhibits the viability of MKN-45 cells with IC50 of less than 1 nM. Treatment with it (as low as 0.1 nM) inhibits HGF-induced NCI-H441 cell migration, whereas concentrations of 100 nM to 1 μM almost completely prevents it.
In vivo	EMD 1214063 treatment, at doses of 10 mg/kg or more, results in more than 90% inhibition of c-Met phosphorylation in Hs746T xenograft tumor for a period of at least 72 hours. This compound induces more than 50% reduction of cyclin D1 expression, which persists after 96 hours upon treatment with doses of 100 mg/kg. A transient induction of p27 and cleaved caspase-3 are also observed upon treatment with this chemical. It (15 mg/kg, daily) treatment induces complete regression of gastric carcinoma xenografts Hs746T, in which c-Met is amplified, overexpressed, and activated in a ligand-independent fashion.
Referenser	[1] https://pubmed.ncbi.nlm.nih.gov/23553846/

Applikationer (Applications)

Metoder	Biomarkörer	Bilder	PMID
Western blot	p-Met / Met / p-ERK / ERK / p-AKT / AKT		26006023
Growth inhibition assay	Cell viability		26006023

Klinisk prövningsinformation (Clinical Trial Information)

(data från https://clinicaltrials.gov, uppdaterad den 2024-05-22)

NCT-nummer	Rekrytering	Tillstånd	Sponsor/Samarbetspartners	Startdatum	Faser
NCT05782361	Recruiting	Advanced Cancer\|Non Small Cell Lung Cancer	Institute of Cancer Research United Kingdom\|Merck Serono GmbH Germany\|Merck Sharp & Dohme LLC	May 3 2023	Phase 1
NCT05120960	Withdrawn	Brain Tumor	M.D. Anderson Cancer Center	February 27 2023	Phase 1
NCT04739358	Terminated	Advanced Non-Small Cell Lung Cancer With MET Mutations	Criterium Inc.\|EMD Serono Research & Development Institute Inc.	May 25 2022	Phase 1\|Phase 2
NCT05203822	Completed	Healthy	Merck Healthcare KGaA Darmstadt Germany an affiliate of Merck KGaA Darmstadt Germany	January 21 2022	Phase 1
NCT05213481	Completed	Healthy	Merck Healthcare KGaA Darmstadt Germany an affiliate of Merck KGaA Darmstadt Germany	December 15 2021	Phase 1
NCT04204902	Completed	Healthy	Merck Healthcare KGaA Darmstadt Germany an affiliate of Merck KGaA Darmstadt Germany	October 17 2019	Phase 1

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Tepotinib (EMD-1214063) c-Met Hämmare

Molekylvikt: 492.57

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Tepotinib (EMD-1214063) c-Met Hämmare

Molekylvikt: 492.57

Kvalitetskontroll (Quality Control)

Cellodling, behandling & arbetskoncentration (Cell Culture, Treatment & Working Concentration)

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Löslighet (Solubility)

Molaritetsräknare

In vivo-formuleringsräknare (Klar lösning)

Verkningsmekanism (Mechanism of Action)

Applikationer (Applications)

Klinisk prövningsinformation (Clinical Trial Information)

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)