BMS-777607
别名: BMS 817378
BMS-777607 (BMS 817378)是一种Met相关的抑制剂，作用于c-Met，Axl，Ron和Tyro3，在无细胞试验中IC50分别为3.9 nM，1.1 nM，1.8 nM和4.3 nM，作用于Met相关靶点比作用于Lck， VEGFR-2，和TrkA/B选择性高40倍，比作用于其他受体和非受体激酶选择性高500多倍。
BMS-777607 Chemical Structure
CAS: 1025720-94-8
产品质控
批次：
纯度：
99.64%
99.64
BMS-777607相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| T-47D | Function assay | 10 μM | Induces polyploidy by 86 % | 23468529 | |
| ZR-75-1 | Growth inhibitory assay | ~5 μM | inhibits cell proliferation | 23468529 | |
| T-47D | Growth inhibitory assay | ~5 μM | inhibits cell proliferation | 23468529 | |
| KHT | Growth inhibitory assay | ~10 μM | inhibits KHT cell proliferation | 22286523 | |
| KHT | Function assay | ~0.5 μM | inhibits cell invasion | 22286523 | |
| KHT | Function assay | ~0.5 μM | inhibits cell migration | 22286523 | |
| KHT | Function assay | ~1 μM | prevents spontaneous KHT cell scattering with IC50 of 0.1-0.5 μM | 22286523 | |
| PC-3 | Growth inhibitory assay | ~10 μM | reduces cell proliferation | 20515943 | |
| DU145 | Function assay | 0.1 μM | impairs HGF-mediated cell invasion | 20515943 | |
| PC-3 | Function assay | 0.1 μM | impairs HGF-mediated cell invasion | 20515943 | |
| DU145 | Function assay | 0.01 μM | suppresses HGF-induced cell migration | 20515943 | |
| PC-3 | Function assay | 0.01 μM | suppresses HGF-induced cell migration | 20515943 | |
| DU145 | Function assay | 0.1 μM | exhibits inhibitory effect on HGF-induced cell scattering | 20515943 | |
| PC-3 | Function assay | 0.1 μM | exhibits inhibitory effect on HGF-induced cell scattering | 20515943 | |
| ZR-75-1 | Function assay | 10 μM | Induces polyploidy by 88% | 23468529 | |
| T-47D | Function assay | 10 μM | inhibits AURK-B function and induces its protein degradation | 23468529 | |
| CHRF | Function assay | 10 μM | inhibits cell division | 25304900 | |
| HPDE | Function assay | 10 μM | blocks constitutive activation and decreased AKT signaling | 26477314 | |
| U118MG | Kinase assay | ~3 μM | blocks AXL phosphorylation | 26848524 | |
| SF126 | Kinase assay | ~3 μM | blocks AXL phosphorylation | 26848524 | |
| U118MG | Cytoxicity assay | 12.5 μM | decreases glioma cell viability | 26848524 | |
| SF126 | Cytoxicity assay | 12.5 μM | decreases glioma cell viability | 26848524 | |
| U118MG | Apoptosis assay | 12.5 μM | induces glioma cell apoptosis | 26848524 | |
| SF126 | Apoptosis assay | 12.5 μM | induces glioma cell apoptosis | 26848524 | |
| U118MG | Function assay | 12.5 μM | blocks glioma cell migration and invasive growth pattern | 26848524 | |
| SF126 | Function assay | 12.5 μM | blocks glioma cell migration and invasive growth pattern | 26848524 | |
| GTL16 | Function assay | 6.25 mg/kg | Cmax in human GTL16 cells xenografted athymic mouse at 6.25 mg/kg, po, Cmax = 4.5 μM. | 19260711 | |
| GTL16 | Function assay | 50 mg/kg | Cmax in human GTL16 cells xenografted athymic mouse at 50 mg/kg, po, Cmax = 43.7 μM. | 19260711 | |
| GTL16 | Function assay | 30 mins | Inhibition of Met phosphorylation in human GTL16 cells after 30 mins, IC50 = 0.02 μM. | 19260711 | |
| GTL16 | Antiproliferative assay | 72 hrs | Antiproliferative activity against Met-dependent human GTL16 cells after 72 hrs by MTS assay, IC50 = 0.1 μM. | 19260711 | |
| NCI-H1993 | Antiproliferative assay | 72 hrs | Antiproliferative activity against Met-dependent human NCI-H1993 cells after 72 hrs by MTS assay, IC50 = 0.15 μM. | 19260711 | |
| U87 | Antiproliferative assay | 72 hrs | Antiproliferative activity against Met-driven human U87 cells after 72 hrs by MTS assay, IC50 = 0.16 μM. | 19260711 | |
| BAF3 | Cytotoxicity assay | 72 hrs | Cytotoxicity against mouse BAF3 cells expressing TPR-Met assessed as growth inhibition after 72 hrs, IC50 = 0.1884 μM. | 24792774 | |
| DU145 | Antiinvasive assay | 1 hr | Antiinvasive activity in human DU145 cells assessed as inhibition of HGF-induced cell motility preincubated for 1 hr before HGF treatment measured after 24 hrs by cell scattering assay, IC50 = 0.2 μM. | 24900830 | |
| MKN45 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human MKN45 cells assessed as growth inhibition after 72 hrs, IC50 = 0.2858 μM. | 24792774 | |
| NCI-H1993 | Cytotoxicity assay | 48 hrs | Cytotoxicity against human NCI-H1993 cells after 48 hrs by MTT assay, IC50 = 1.108 μM. | 24900830 | |
| MGHU3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human MGHU3 cells after 72 hrs by CellTiter-Glo assay | 30309671 | |
| RT112 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human RT112 cells after 72 hrs by CellTiter-Glo assay | 30309671 | |
| KHT | Kinase assay | blocks the c-Met signaling pathway with IC50 of 10 nM | 22286523 | ||
| 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 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells | 29435139 | ||
| LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells | 29435139 | ||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | BMS-777607 (BMS 817378)是一种Met相关的抑制剂，作用于c-Met，Axl，Ron和Tyro3，在无细胞试验中IC50分别为3.9 nM，1.1 nM，1.8 nM和4.3 nM，作用于Met相关靶点比作用于Lck， VEGFR-2，和TrkA/B选择性高40倍，比作用于其他受体和非受体激酶选择性高500多倍。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 特性 | BMS 777607是有效的Met家族成员抑制剂，比作用于Lck, VEGFR-2,和TrkA/B的选择性高40多倍，比作用同样其他受体和非受体激酶选择性高500多倍。 | |||||||||||
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | BMS-777607是ATP竞争性Met激酶选择性抑制剂，有效抑制c-Met自磷酸化，作用于GTL-16细胞裂解物， IC50为20 nM，且选择性抑制Met驱动的肿瘤细胞系如GTL-16细胞系, H1993和 U87增殖。[1] BMS-777607 作用于DU145前列腺癌细胞，抑制肝细胞生长因子 (HGF)引起的c-Met自磷酸化， IC50<1 nM 。BMS 777607对肿瘤细胞生长作用效果不大，但是作用于PC-3 和DU145 细胞，抑制HGF诱导的细胞分散。BMS 777607作用于这两种细胞，也抑制刺激的细胞迁移和入侵，IC50<0.1 μM，这种作用存在剂量依赖性。[2] BMS 777607(~10 μM)作用于高度转移性鼠科KHT细胞2小时，有效清除自磷酸化的c-Met水平，IC50为10 nM，不影响全部 c-Met,导致下游信号分子包括 ERK, Akt, p70S6K 和 S6受抑制，这种作用存在剂量依赖性。纳摩尔级BMS-777607(~1 μM)处理24小时,有效抑制KHT细胞分散，活动，和入侵，这与MET基因抑制相关,适当影响细胞增殖和集落形成。[3] |
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|---|---|---|---|---|
| 细胞实验 | 细胞系 | 啮齿类纤维肉瘤KHT细胞 | ||
| 浓度 | 溶于DMSO，作为储存液(10 mM), 终浓度为10 μM 左右 | |||
| 孵育时间 | 2, 24和96小时 | |||
| 方法 | 用连续稀释的BMS 777607 处理KHT细胞96小时，然后进行MTT实验和台酚蓝排除，分别测定细胞增殖和细胞死亡。KHT细胞集落和BMS 777607温育24小时，然后用结晶紫(0.1%)染色，然后显影，测定细胞分散情况。使用无菌的1 ml吸管端在融合的KHT单层细胞上划2 mm 痕，随后用BMS-777607处理24小时，在4块随机区域中计数迁移到剥蚀地细胞数，用于测定细胞迁移情况。为了测定细胞入侵，用Matrigel预包被的转移嵌入板(8 μm 孔膜)，和无血清培养基在有或无BMS 777607存在时，在37oC下温育2小时,使Matrigel再水化。悬浮在无血清培养基上的细胞装到小室顶端，悬浮在含10% FBS的完全培养基上的细胞装到小室底端，作为化学引诱物。温育24小时，移除 Matrigel，用结晶紫染色。显影并计数在滤液下面的入侵细胞。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p53 / p21 / Survivin / p-Rb / Rb p-c-Met / c-Met / p-FAK / p-c-Src / p-Akt / p-S6K / p-S6 |
|
24444656 | |
| Immunofluorescence | α-tubulin / survivin |
|
24444656 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | BMS 777607按6.25-50 mg/kg剂量口服处理给药携带GTL-16人类移植瘤的无胸腺小鼠，明显降低肿瘤体积，且没有毒性。[1] BMS 777607按25 mg/kg剂量每天处理6-8周大的注射啮齿类纤维肉瘤KHT细胞的雌性C3H/HeJ小鼠，降低 KHT肺肿瘤结节数量,提高形态出血, 且明显修复损害转移表型，与对照组相比，没有明显毒性。BMS 777607按 10 mg/kg 低剂量处理，也适度但不显著抑制肺结节形成。[3] |
|
|---|---|---|
| 动物实验 | Animal Models | 携带啮齿类纤维肉瘤KHT细胞的雌性C3H/HeJ小鼠 |
| Dosages | 10-25 mg/kg | |
| Administration | 饲喂处理，每天一次 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01721148 | Completed | Malignant Solid Tumour |
ASLAN Pharmaceuticals |
October 2012 | Phase 1 |
| NCT00605618 | Completed | Advanced Solid Tumors |
Bristol-Myers Squibb |
March 2008 | Phase 1|Phase 2 |
化学信息&溶解度
| 分子量 | 512.89 | 分子式 | C25H19ClF2N4O4 |
| CAS号 | 1025720-94-8 | SDF | Download BMS-777607 SDF |
| Smiles | CCOC1=C(C(=O)N(C=C1)C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C(=NC=C4)N)Cl)F | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 100 mg/mL ( (194.97 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
|
体内溶解配方 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | |||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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常见问题及建议解决方法
问题 1:
What formulation can we use to dissolve S1561 for mice in vivo study?
回答：
S1561 BMS-777607 in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30 mg/ml is a suspension. It is fine for oral gavage. If you are going to use it for injection, please try the following vehicle: 4% DMSO+30% PEG 300+ddH2O. BMS-777607 can be dissolved in it at 5 mg/ml as a clear solution.
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