BMS-777607
(Synonyms: N-[4-[(2-氨基-3-氯吡啶-4-基)氧基]-3-氟苯基]-4-乙氧基-1-(4-氟苯基)-2-氧代-1,2-二氢吡啶-3-甲酰胺,BMS 817378) 目录号 : GC14214
BMS-777607 是一种泛 TAM 抑制剂，对不同类型的癌症显示出抗肿瘤活性。
Cas No.:1025720-94-8
Sample solution is provided at 25 µL, 10mM.
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BMS-777607 is a pan-TAM inhibitor, which shows anti-tumor activity to different types of cancer. BMS-777607 could also enhance the expression of proinflammatory cytokines and pro-immune cells over control with the combination anti-PD-1 treatment. The addition of BMS-777607 to anti- PD-1 treatment down-regulated immunosuppressive cytokines expression in tumor microenvironment. It has been reported that the combined treatment of BMS-777607 with anti-PD-1significantly decreased tumor growth and incidence of lung metastasis [1]
In vitro and in vivo experiment demonstrate that BMS-777607 could inhibit the growth of human CCA cells and decrease the expression of phospho-RON. Moreover, in HuCCT1 and KKU-100 cell lines, IC50 values after treatment with BMS-777607 for 6 days were 11.4 and 5.9 μM, respectively. BMS-777607 could also inhibit the in vivo growth of CCA in rats. [2]
References:
[1].Kasikara C, et al. Pan-TAM Tyrosine Kinase Inhibitor BMS-777607 Enhances Anti-PD-1 mAb Efficacy in a Murine Model of Triple-Negative Breast Cancer. Cancer Res. 2019 May 15;79(10):2669-2683.
[2].Cheng CT, et al. MET-RON dual inhibitor, BMS-777607, suppresses cholangiocarcinoma cell growth, and MET-RON upregulation indicates worse prognosis for intra-hepatic cholangiocarcinoma patients. Oncol Rep. 2018 Sep;40(3):1411-1421.
BMS-777607 是一种泛 TAM 抑制剂，对不同类型的癌症显示出抗肿瘤活性。 BMS-777607 还可以通过联合抗 PD-1 治疗增强促炎细胞因子和促免疫细胞的表达。在抗 PD-1 治疗中加入 BMS-777607 可下调肿瘤微环境中的免疫抑制细胞因子表达。据报道，BMS-777607 与抗 PD-1 联合治疗可显着降低肿瘤生长和肺转移发生率[1]
体外和体内实验表明，BMS-777607 可以抑制人 CCA 细胞的生长并降低磷酸化 RON 的表达。此外，在 HuCCT1 和 KKU-100 细胞系中，用 BMS-777607 处理 6 天后的 IC50 值分别为 11.4 和 5.9 μM。 BMS-777607 还可以抑制大鼠体内 CCA 的生长。 [2]
| Cell experiment [1]: | |
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Cell lines |
CCA cell lines HuCCT1, KKU-100 |
|
Preparation Method |
The HuCCT1 cells were cultured in RPMI-1640 medium. The KKU-100 cells were cultured in DMEM. All the cells were supplemented with 10% heat-inactivated FBS, 100 μg/ml streptomycin, 100 μg/ml penicillin, and 2 mM L glutamine in a humidified atmosphere containing 5% CO2 at 37˚C. |
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Reaction Conditions |
Clonogenic assays were used to measure the growth of the HuCCT1 and KKU-100 cell lines, in the presence of varying concentrations of BMS 777607(1/3/5/10 μM). |
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Applications |
BMS-777607 showed a concentration-dependent antiproliferative effect on both the HuCCT1 and KKU-100 cell lines. Moreover, in HuCCT1 and KKU-100 cell lines, IC50 values after treatment with BMS-777607 for 6 days were 11.4 and 5.9 μM, respectively. In addition, the expression of phospho-RON was decreased in both HuCCT1 and KKU-100 cell lines after treatment with BMS-777607. |
| Animal experiment [1]: | |
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Animal models |
adult male Sprague Dawley (SD) rats (310±14 g) |
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Preparation Method |
The rats were administered 300 mg/l thioacetamide (TAA) via drinking water daily for up to 20 weeks. The gemcitabine/Oxaliplat -in treatment group received gemcitabine [50 mg/kg, intraperitoneal injection(i.p.)] and oxaliplatin (2 mg/kg, i.p.) once every 2 weeks over a 4-week period starting at the 21st week. The BMS-777607 treatment group received BMS-777607 [30 mg/kg, per os (p.o.)] 5 days/week starting at the 21st week. The control group rats received i.p. injections of PBS following the same schedule. |
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Dosage form |
30 mg/kg, per os (p.o.) |
|
Applications |
BMS-777607 could significantly suppress the in vivo growth of CCA tumors in animal model. |
|
References: [1]. Cheng CT, et al. MET-RON dual inhibitor, BMS-777607, suppresses cholangiocarcinoma cell growth, and MET-RON upregulation indicates worse prognosis for intra-hepatic cholangiocarcinoma patients. Oncol Rep. 2018 Sep;40(3):1411-1421. |
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| Cas No. | 1025720-94-8 | SDF | |
| 别名 | N-[4-[(2-氨基-3-氯吡啶-4-基)氧基]-3-氟苯基]-4-乙氧基-1-(4-氟苯基)-2-氧代-1,2-二氢吡啶-3-甲酰胺,BMS 817378 | ||
| 化学名 | N-[4-(2-amino-3-chloropyridin-4-yl)oxy-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide | ||
| Canonical 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 | ||
| 分子式 | C25H19ClF2N4O4 | 分子量 | 512.89 |
| 溶解度 | ≥ 25.65mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9497 mL | 9.7487 mL | 19.4974 mL |
| 5 mM | 0.3899 mL | 1.9497 mL | 3.8995 mL |
| 10 mM | 0.195 mL | 0.9749 mL | 1.9497 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet