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Protein Tyrosine Kinase
c-Met inhibitor
-
Axl inhibitor
-
Tyro3 inhibitor
-
RON inhibitor
BMS-777607
僅限科研使用
BMS-777607
別名: BMS 817378
BMS-777607 (BMS 817378)是一種Met相關(guān)的抑制劑，作用于c-Met，Axl，Ron和Tyro3，在無細胞試驗中IC50分別為3.9 nM，1.1 nM，1.8 nM和4.3 nM，作用于Met相關(guān)靶點比作用于Lck， VEGFR-2，和TrkA/B選擇性高40倍，比作用于其他受體和非受體激酶選擇性高500多倍。
BMS-777607 Chemical Structure
CAS: 1025720-94-8
產(chǎn)品質(zhì)控
批次：
純度：
99.64%
99.64
BMS-777607相關(guān)產(chǎn)品
相關(guān)信號通路圖
細胞實驗數(shù)據(jù)示例
| 細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息 |
|---|---|---|---|---|---|
| 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 | ||
| 點擊查看更多細胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | BMS-777607 (BMS 817378)是一種Met相關(guān)的抑制劑，作用于c-Met，Axl，Ron和Tyro3，在無細胞試驗中IC50分別為3.9 nM，1.1 nM，1.8 nM和4.3 nM，作用于Met相關(guān)靶點比作用于Lck， VEGFR-2，和TrkA/B選擇性高40倍，比作用于其他受體和非受體激酶選擇性高500多倍。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 特性 | BMS 777607是有效的Met家族成員抑制劑，比作用于Lck, VEGFR-2,和TrkA/B的選擇性高40多倍，比作用同樣其他受體和非受體激酶選擇性高500多倍。 | |||||||||||
| 靶點 |
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| 體外研究(In Vitro) | ||||
| 體外研究活性 | BMS-777607是ATP競爭性Met激酶選擇性抑制劑，有效抑制c-Met自磷酸化，作用于GTL-16細胞裂解物， IC50為20 nM，且選擇性抑制Met驅(qū)動的腫瘤細胞系如GTL-16細胞系, H1993和 U87增殖。[1] BMS-777607 作用于DU145前列腺癌細胞，抑制肝細胞生長因子 (HGF)引起的c-Met自磷酸化， IC50<1 nM 。BMS 777607對腫瘤細胞生長作用效果不大，但是作用于PC-3 和DU145 細胞，抑制HGF誘導的細胞分散。BMS 777607作用于這兩種細胞，也抑制刺激的細胞遷移和入侵，IC50<0.1 μM，這種作用存在劑量依賴性。[2] BMS 777607(~10 μM)作用于高度轉(zhuǎn)移性鼠科KHT細胞2小時，有效清除自磷酸化的c-Met水平，IC50為10 nM，不影響全部 c-Met,導致下游信號分子包括 ERK, Akt, p70S6K 和 S6受抑制，這種作用存在劑量依賴性。納摩爾級BMS-777607(~1 μM)處理24小時,有效抑制KHT細胞分散，活動，和入侵，這與MET基因抑制相關(guān),適當影響細胞增殖和集落形成。[3] |
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|---|---|---|---|---|
| 細胞實驗 | 細胞系 | 嚙齒類纖維肉瘤KHT細胞 | ||
| 濃度 | 溶于DMSO，作為儲存液(10 mM), 終濃度為10 μM 左右 | |||
| 孵育時間 | 2, 24和96小時 | |||
| 方法 | 用連續(xù)稀釋的BMS 777607 處理KHT細胞96小時，然后進行MTT實驗和臺酚藍排除，分別測定細胞增殖和細胞死亡。KHT細胞集落和BMS 777607溫育24小時，然后用結(jié)晶紫(0.1%)染色，然后顯影，測定細胞分散情況。使用無菌的1 ml吸管端在融合的KHT單層細胞上劃2 mm 痕，隨后用BMS-777607處理24小時，在4塊隨機區(qū)域中計數(shù)遷移到剝蝕地細胞數(shù)，用于測定細胞遷移情況。為了測定細胞入侵，用Matrigel預包被的轉(zhuǎn)移嵌入板(8 μm 孔膜)，和無血清培養(yǎng)基在有或無BMS 777607存在時，在37oC下溫育2小時,使Matrigel再水化。懸浮在無血清培養(yǎng)基上的細胞裝到小室頂端，懸浮在含10% FBS的完全培養(yǎng)基上的細胞裝到小室底端，作為化學引誘物。溫育24小時，移除 Matrigel，用結(jié)晶紫染色。顯影并計數(shù)在濾液下面的入侵細胞。 |
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| 實驗圖片 | 檢測方法 | 檢測指標 | 實驗圖片 | PMID |
| Western blot | p-c-Met / c-Met / p-FAK / p-c-Src / p-Akt / p-S6K / p-S6 p53 / p21 / Survivin / p-Rb / Rb |
|
22639908 | |
| Immunofluorescence | α-tubulin / survivin |
|
24444656 | |
| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | BMS 777607按6.25-50 mg/kg劑量口服處理給藥攜帶GTL-16人類移植瘤的無胸腺小鼠，明顯降低腫瘤體積，且沒有毒性。[1] BMS 777607按25 mg/kg劑量每天處理6-8周大的注射嚙齒類纖維肉瘤KHT細胞的雌性C3H/HeJ小鼠，降低 KHT肺腫瘤結(jié)節(jié)數(shù)量,提高形態(tài)出血, 且明顯修復損害轉(zhuǎn)移表型，與對照組相比，沒有明顯毒性。BMS 777607按 10 mg/kg 低劑量處理，也適度但不顯著抑制肺結(jié)節(jié)形成。[3] |
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|---|---|---|
| 動物實驗 | Animal Models | 攜帶嚙齒類纖維肉瘤KHT細胞的雌性C3H/HeJ小鼠 |
| Dosages | 10-25 mg/kg | |
| Administration | 飼喂處理，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 |
化學信息&溶解度
| 分子量 | 512.89 | 分子式 | C25H19ClF2N4O4 |
| CAS號 | 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 | ||
| 儲存條件(自收到貨起) | |||
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體外溶解度 |
DMSO : 100 mg/mL ( (194.97 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO) Water : Insoluble Ethanol : 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 | ||||
實驗計算
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）
mg/kg
g
μL
只
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）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
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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常見問題及建議解決方法
問題 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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