产品说明书
JNJ-38877605
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同义名 : | - |
| CAS号 : | 943540-75-8 | |
| 货号 : | A275907 | |
| 分子式 : | C19H13F2N7 | |
| 纯度 : | 98+% | |
| 分子量 : | 377.35 | |
| MDL号 : | MFCD11977274 | |
| 存储条件： |
粉末 Inert atmosphere,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 30 mg/mL(79.5 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
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| 动物实验配方： |
30% propylene glycol+5% Tween 80+65% water 30 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 描述 | The receptor tyrosine kinase c-Met, also known as receptor of hepatocyte growth factor (HGF) and scatter factor, plays an important role in physiologic processes such as embryologic development, wound healing, tissue regeneration, angiogenesis, cell growth, local invasion, and morphogenetic differentiation[3]. And its downstream v-akt murine thymoma viral oncogene homolog (AKT) and mitogen-activated protein kinase (ERK) pathways are regulated by HGF/c-MET. The HGF/c-MET axis is involved in cancer progression, metastasis, and acquired resistance[4]. JNJ-38877605 is an orally available, nanomolar active and highly selective c-Met ATP-competitive kinase inhibitor with IC50 of 4.7 nM for c-Met kinase, which induces cell death in tumor cells overexpressing c-MET protein or expressing constitutively activated c-MET protein, and it also can suppress the phosphorylation of Ron[5]. After JNJ-38877605 totally was dosed 200, 300 and 350 mg/kg per week for 1 month at rabbits, renal toxicity had been observed[6]. In an experiment, a kind of deuterated JNJ-38877605 was administrated 10 mg/kg to cynomolgus monkeys, suggesting that deuterated JNJ-38877605 displayed diminished renal toxicity[7]. In a vitro study, EBC1 (NSCLCs), GTL16, NCI-H1993, and MKN45 (gastric adenocarcinomas) cell lines were treated with c-Met selective inhibitor JNJ-38877605 at a dose of 500 nM for 2h, as it is expected that JNJ-38877605 caused a significant reduction of Met phosphorylation[5]. In a vivo study, JNJ-3887760 were used to treat renal CSCs (cancer stem cells) mice implanted with a human bone at a dose of 40 mg/kg for 60 days, and it was showed that JNJ-38877605 inhibited the activation of osteoclasts induced by RCC stem cells and it stimulated osteoblast activity, finally resulting in a reduction of bone turnover consistent with the inhibition of bone metastases[8]. | ||
| 作用机制 | JNJ-38877605 binds to the ATP-binding site of c-Met kinase with a high affinity. | ||
| 细胞研究 | |||||
|---|---|---|---|---|---|
| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
| human EBC1 cells | Proliferation assay | 72 h | Antiproliferative activity against human EBC1 cells after 72 hrs, IC50=9.5 nM | 26005523 | |
| human MKN45 cells | Proliferation assay | 72 h | Antiproliferative activity against human MKN45 cells after 72 hrs, IC50=10.9 nM | 26005523 | |
| human SNU5 cells | Proliferation assay | 72 h | Antiproliferative activity against human SNU5 cells after 72 hrs, IC50=15.8 nM | 26005523 | |
| 临床研究 | |||||
|---|---|---|---|---|---|
| NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
| NCT00651365 | Neoplasms | Phase 1 | Terminated(Early termination d... 展开 >>ue to increase in serum creatinine levels and minimal PD activity.) 收起 << | - | - |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.65mL 0.53mL 0.27mL |
13.25mL 2.65mL 1.33mL |
26.50mL 5.30mL 2.65mL |
| 参考文献 |
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