Ripretinib (DCC-2618) was designed to inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative neoplasms, particularly in gastrointestinal stromal tumors (GISTs), in which the heterogeneity of drug-resistant KIT mutations is a major challenge. Ripretinib is a "switch-control" kinase inhibitor that forces the activation loop (or activation "switch") into an inactive conformation. Ripretinib inhibits all tested KIT and PDGFRA mutants, and notably is a type II kinase inhibitor demonstrated to broadly inhibit activation loop mutations in KIT and PDGFRA, previously thought only achievable with type I inhibitors. Ripretinib shows efficacy in preclinical cancer models, and preliminary clinical data provide proof-of-concept that ripretinib inhibits a wide range of KIT mutants in patients with drug-resistant GISTs.

中文翻译：

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瑞普替尼（DCC-2618）是一种广泛的致癌和耐药KIT和PDGFRA变体的开关控制激酶抑制剂。

利普替尼（DCC-2618）被设计用来抑制在癌症和骨髓增生性肿瘤中，特别是在胃肠道间质瘤（GIST）中发现的突变KIT和PDGFRA激酶的全谱，其中耐药性KIT突变的异质性是一个主要挑战。瑞普替尼是一种“开关控制”激酶抑制剂，可将激活环（或激活“开关”）强制变为无活性构象。瑞普替尼抑制所有测试的KIT和PDGFRA突变体，尤其是II型激酶抑制剂，被证明可广泛抑制KIT和PDGFRA中的活化环突变，以前认为只能通过I型抑制剂才能实现。利普替尼在临床前癌症模型中显示功效，