Home Protein Tyrosine Kinase c-Met inhibitor Tepotinib (EMD-1214063)

연구용

Tepotinib (EMD-1214063) c-Met inhibitor

제품 번호: S7067

Tepotinib is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. Tepotinib (EMD 1214063) induces autophagy. Phase 1.
Tepotinib (EMD-1214063) c-Met inhibitor Chemical Structure

화학 구조

분자량: 492.57

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품질 관리 (Quality Control)

배치: 순도: 99.58%
99.58

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 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
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 492.57 화학식

C29H28N6O2

 보관 (수령일로부터)
CAS 번호 1100598-32-0 SDF 다운로드 원액 보관

동의어 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

용해도 (Solubility)

In vitro
배치:

DMSO : 17 mg/mL (34.51 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 6 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
c-Met
(Cell-free assay)
4 nM
시험관 내(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.
생체 내(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.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-Met / Met / p-ERK / ERK / p-AKT / AKT
S7067-WB1
26006023
Growth inhibition assay Cell viability
S7067-viability1
26006023

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
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