Ripretinib
别名: DCC-2618
Ripretinib是一种具有口服活性的Kit (c-Kit)和PDGFR-alpha抑制剂，对WT Kit (c-Kit)、V654A Kit (c-Kit)、T670I Kit (c-Kit)、D816H Kit (c-Kit)和D816V Kit (c-Kit)的IC50分别为4 nM、8 nM、18 nM、5 nM和14 nM。
Ripretinib Chemical Structure
CAS: 1442472-39-0
客户使用Selleck的发表文献7篇
产品质控
Ripretinib相关产品
| 相关产品 | Masitinib Amuvatinib (MP-470) OSI-930 Sitravatinib (MGCD516) ISCK03 PDGFR inhibitor 1 | 点击展开 |
|---|---|---|
| 相关化合物库 | 激酶抑制剂库 酪氨酸激酶抑制剂分子库 PI3K/Akt 抑制剂库 细胞周期化合物库 血管生成相关化合物库 | 点击展开 |
相关信号通路图
c-Kit抑制剂选择性比较
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 |
|---|---|---|---|---|---|
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) and A829P mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.003 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) and N822K mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.004 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.004 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) and D820A mutant and D820A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.006 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.013 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.014 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit V560D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.023 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) and V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.031 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 9 AY502 to 503 insertion mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.034 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit D816V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.037 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant and T670I mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.037 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of TEL-fused PDGFRalpha (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.04 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of TEL-fused PDGFRbeta (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.045 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit V560D/D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.048 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit V560D/V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.075 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 9 AY502 to 503 insertion and D816 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.078 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of KDR (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.098 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 11 deletion (560 to 578 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.13 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of PDGFRalpha V561D/D842V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.188 μM. | 30204441 | |
| Growth inhibition assay | BA/F3 | 72 hrs | Inhibition of Kit exon 9 AY502 to 503 insertion and V654 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.205 μM. | 30204441 | |
| Cytotoxicity assay | BA/F3 | 72 hrs | Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50 = 8.037 μM. | 30204441 | |
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Ripretinib是一种具有口服活性的Kit (c-Kit)和PDGFR-alpha抑制剂，对WT Kit (c-Kit)、V654A Kit (c-Kit)、T670I Kit (c-Kit)、D816H Kit (c-Kit)和D816V Kit (c-Kit)的IC50分别为4 nM、8 nM、18 nM、5 nM和14 nM。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | DCC-2618有效并广泛地抑制KIT原发性和耐药性突变体，如发生在外显子9、11、13、14、17和18的突变，以及发生在PDGFRA外显子12、14、18的原发性突变[3]。DCC-2618以纳摩尔级别的效力抑制多种性质的KIT：WT (IC50 4 nM), V654A (8 nM), T670I (18 nM), D816H (5 nM), D816V (14 nM)。在瞬时转染了KIT原发性突变体和二次突变的CHO细胞中，DCC-2618抑制了外显子17、外显子9/13、外显子9/14，外显子9/17，外显子11/17突变的KIT，包括位于外显子17的D816V, D816G, D820A, D820E, D820Y, N822K, N822Y, N822H和Y823D原发性或二次突变。在MO7e细胞系中，DCC-2618抑制野生型KIT的磷酸化（IC50=36 nM）。在人源GIST细胞系中，包括GIST T1(缺失外显子11)、GIST 430（缺失外显子11/外显子13 V654A）和GIST 48（外显子11 V560D/外显子17 D820A）, DCC-2618也能有效抑制KIT的激活。在小鼠肥大细胞增多症中，DCC-2618可有效抑制P815细胞(表达外显子17 D816Y 突变KIT)的增殖，IC50为2 nM[1]。在多种人类肥大细胞系（HMC-1, ROSA, MCPV-1）和从晚期系统性肥大细胞增多症患者体内分离的原代肿瘤肥大细胞中，DCC-2618可抑制其增殖和生存[2]。 |
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| 细胞实验 | 细胞系 | HMC-1.1, HMC-1.2, ROSA (KIT WT)和 ROSA (KIT D816V)细胞 | ||
| 浓度 | 0.5-5 μM | |||
| 孵育时间 | 4 h | |||
| 方法 | 将细胞培养于对照组培养基中或加入0.5-5 μM DCC-2618，置于37℃培养4小时。结束后，收集细胞提取蛋白质，进行Western blotting分析。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | KIT / BTK STAT5 / AKT / ERK |
|
29439183 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 |
在体内，50 mg/kg DCC-2618可在GIST T1移植瘤模型抑制KIT磷酸化，达到90%的有效剂量（ED90），EC50约为470 ng/mL。每日两次口服给药，DCC-2618可几乎完全地造成肿瘤瘀滞[1]。在移植瘤模型中，DCC-2618可阻止KIT和PFGFRA驱动的肿瘤生长[3]。 |
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|---|---|---|
| 动物实验 | Animal Models | 小鼠移植瘤模型 |
| Dosages | 100 mg/kg/day 或 25 mg/kg/day 或 50 mg/kg BID | |
| Administration | 口服 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT05080621 | Withdrawn | Gastrointestinal Stromal Tumors |
Deciphera Pharmaceuticals LLC |
November 2021 | Phase 1|Phase 2 |
| NCT04633122 | Completed | Gastrointestinal Stromal Tumor(GIST) |
Zai Lab (Shanghai) Co. Ltd.|Zai Lab (Hong Kong) Ltd. |
November 25 2020 | Phase 2 |
| NCT02571036 | Completed | Gastrointestinal Stromal Tumors|Advanced Systemic Mastocytosis|Advanced Cancers |
Deciphera Pharmaceuticals LLC |
November 2015 | Phase 1 |
化学信息&溶解度
| 分子量 | 510.36 | 分子式 | C24H21BrFN5O2 |
| CAS号 | 1442472-39-0 | SDF | -- |
| Smiles | CCN1C2=CC(=NC=C2C=C(C1=O)C3=CC(=C(C=C3Br)F)NC(=O)NC4=CC=CC=C4)NC | ||
| 储存条件(自收到货起) | 3年 -20°C 粉状 | ||
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体外溶解度 |
DMSO : 100 mg/mL ( (195.94 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 |
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体内溶解度 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）
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）
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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