A Met kinase family inhibitor
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]
参考文献:
[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 |
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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.) |
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Applications |
BMS-777607 could significantly suppress the in vivo growth of CCA tumors in animal model. |
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参考文献: [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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