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別名: EMD 1214063, MSC2156119 中文名稱:特泊替尼
Tepotinib是一種有效的,選擇性的c-Met抑制劑,IC50為4 nM,作用于c-Met比作用于IRAK4, TrkA, Axl, IRAK1和Mer選擇性高200倍以上。Tepotinib 可誘導(dǎo)自噬。Phase 1。
Tepotinib Chemical Structure
CAS: 1100598-32-0
細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息 |
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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 |
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 | |
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 | ||
點擊查看更多細胞系數(shù)據(jù) |
產(chǎn)品描述 | Tepotinib是一種有效的,選擇性的c-Met抑制劑,IC50為4 nM,作用于c-Met比作用于IRAK4, TrkA, Axl, IRAK1和Mer選擇性高200倍以上。Tepotinib 可誘導(dǎo)自噬。Phase 1。 | ||
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靶點 |
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體外研究(In Vitro) | ||||
體外研究活性 | EMD 1214063抑制A549細胞中HGF誘導(dǎo)的c-Met磷酸化,IC50為6 nM。EMD 1214063治療誘導(dǎo)EBC-1細胞中c-Met組成的磷酸化顯著減少,IC50為9 nM。EMD 1214063有效阻斷c-Met酶主要下游效應(yīng)蛋白的磷酸化,比如Grb2,Gab1,Sos,PLCγ,和磷脂酰肌醇3激酶,在EBC-1,MKN-45,和Hs746T細胞中,范圍為1到10 nM。EMD 1214063大大抑制MKN-45細胞的活性,IC50低于1 nM。用EMD 1214063 (0.1 nM)處理會抑制HGF誘導(dǎo)的NCI-H441細胞移行,而100 nM到1 μM的濃度幾乎對其完全抑制。[1] | |||
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實驗圖片 | 檢測方法 | 檢測指標(biāo) | 實驗圖片 | PMID |
Western blot | p-Met / Met / p-ERK / ERK / p-AKT / AKT | 26006023 | ||
Growth inhibition assay | Cell viability | 26006023 |
體內(nèi)研究(In Vivo) | ||
體內(nèi)研究活性 | EMD 1214063以10毫克/千克或更高的劑量治療,導(dǎo)致Hs746T異種移植腫瘤中超過90%的c-Met磷酸化至少在72小時內(nèi)被抑制。EMD 1214063誘導(dǎo)細胞周期蛋白D1的表達減少50%以上,在100毫克/千克劑量下處理,該作用能夠持續(xù)96小時以上。EMD 1214063處理后,也能觀察到短暫的p27感應(yīng)和裂解的胱天蛋白酶-3。EMD 1214063 (15 毫克/千克,每天)治療誘導(dǎo)c-Met擴增,過度表達,并以配體無關(guān)的方式被激活的胃癌異種移植物Hs746T完全消退。[1] | |
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動物實驗 | Animal Models | 人胃癌異種移植EJ6 |
Dosages | 15毫克/千克 | |
Administration | 每天 |
NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
---|---|---|---|---|---|
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 |
分子量 | 492.57 | 分子式 | C29H28N6O2 |
CAS號 | 1100598-32-0 | SDF | Download Tepotinib SDF |
Smiles | CN1CCC(CC1)COC2=CN=C(N=C2)C3=CC=CC(=C3)CN4C(=O)C=CC(=N4)C5=CC=CC(=C5)C#N | ||
儲存條件(自收到貨起) | |||
體外溶解度 |
DMSO : 17 mg/mL ( (34.51 mM) ;DMSO吸濕會降低化合物溶解度,請使用新開封DMSO) Ethanol : 6 mg/mL (12.18 mM) Water : Insoluble |
摩爾濃度計算器 |
體內(nèi)溶解度 現(xiàn)配現(xiàn)用,請按從左到右的順序依次添加,澄清后再加入下一溶劑 |
動物體內(nèi)配方計算器 |
動物體內(nèi)配方計算器(澄清溶液)
第一步:請輸入基本實驗信息(考慮到實驗過程中的損耗,建議多配一只動物的藥量)
第二步:請輸入動物體內(nèi)配方組成(配方適用于不溶于水的藥物;不同批次藥物配方比例不同,請聯(lián)系Selleck為您提供正確的澄清溶液配方)
計算結(jié)果:
工作液濃度: mg/ml;
DMSO母液配制方法: mg 藥物溶于μL DMSO溶液(母液濃度mg/mL,注:如該濃度超過該批次藥物DMSO溶解度,請先聯(lián)系Selleck);
體內(nèi)配方配制方法:取μL DMSO母液,加入μL PEG300,混勻澄清后加入μL Tween 80,混勻澄清后加入μL ddH2O,混勻澄清。
體內(nèi)配方配制方法:取μL DMSO母液,加入μL Corn oil,混勻澄清。
注意:1. 首先保證母液是澄清的;
2.一定要按照順序依次將溶劑加入,進行下一步操作之前必須保證上一步操作得到的是澄清的溶液,可采用渦旋、超聲或水浴加熱等物理方法助溶。
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