RPI-1是一种细胞渗透性，基于吲哚酮的ATP竞争性酪氨酸激酶抑制剂，已知靶向Ret，EGFR和Met。致瘤性，运动性和侵袭性增加已被描述为肿瘤细胞中HGF / Met失调的生物学结果，因此RPI-1处理H460细胞导致集落数和大小均大大降低。该化合物对小鼠NSCLC H460异种移植瘤和转移模型也具有活性。从机理上讲，RPI-1抑制Tyr1234 / Tyr1235的Met磷酸化，已知该蛋白会激活内在的激酶活性。 RPI-1 is a cell-permeable, indolinone-based ATP-competitive tyrosine kinase inhibitor that is known to target Ret, EGFR, and Met. Increased tumorigenicity, motility, and invasiveness have been described as biological consequences of HGF/Met deregulation in tumor cells, thus RPI-1 treatment of H460 cells resulted in a strong reduction of both colony number and size. The compound is also active at mouse NSCLC H460 xenograft tumor and metastasis model. Mechanistically RPI-1 inhibits Met phosphorylation at Tyr1234/Tyr1235, known to activate the intrinsic kinase activity. Selectively reverts the morphologic phenotype of ret oncogene- (PTC1 & MEN2A), but not H-Ras-, and transformed NIH3T3 in a reversible manner. RPI-1 effectively inhibits the autophosphorylation of PTC1, MEN2A, and Met against Met in N592 in cancer cells, and concomitant receptor down-regulation has also been reported to occur in NIH3T3MEN2A and in small cell lung carcinoma cell line N592.