RAS-RAF pathway presents a valuable target for the cancer treatment due to its important roles in the regulation of tumor proliferation, apoptosis and the obtained resistance. To explore such target a RAS/CRAF interference agent, was therefore conjugated with Pt(IV) prodrugs via ester bond, resulting in total eleven multifunctional Pt(IV) complexes. The complexes could target genomic DNA and disrupt the signaling transduction from RAS protein to CRAF so that block the mitogen-activated protein kinase (MAPK) signaling pathway. Experiments in vitro indicated that all of the Pt(IV) complexes showed potent anti-tumor activity with IC₅₀ values ranged from 8 nM to 22.55 μM, which were significantly improved as compared with cisplatin (CDDP) whose IC₅₀ values ranged from 5.45 μM to 9.05 μM. Among them, 26 exerted the best anti-tumor activity in vitro, which not only exhibited excellent cytotoxicity against normal tumor cells, but also against CDDP-resistance cell lines (e.g. A549/CDDP and SKOV-3/CDDP). Importantly, 26 only showed little effect on normal cell lines such as HUEVC and LO2. Besides, the following biological mechanisms studies demonstrated that 26 could efficiently enter.

A549 cells, significantly arrest cell cycle at G2/M phase, disrupt the signaling pathway and trigger endogenous caspase apoptosis pathway. Furthermore, results of a xenograft subcutaneous model of A549 tumor showed that 26 could effectively decrease tumor growth rates without causing loss of bodyweight.

RAS-RAF途径由于其在调节肿瘤增殖，凋亡和获得的抗性中的重要作用而成为癌症治疗的重要靶标。为了探索这种靶标，RAS / CRAF干扰剂因此通过酯键与Pt（IV）前药缀合，从而形成总共11种多功能Pt（IV）复合物。该复合物可以靶向基因组DNA，并破坏从RAS蛋白到CRAF的信号转导，从而阻断有丝分裂原激活的蛋白激酶（MAPK）信号通路。体外实验表明，所有Pt（IV）配合物均显示有效的抗肿瘤活性，IC ₅₀值在8 nM至22.55μM之间，与顺铂（CDDP）的IC _50值相比有显着改善值范围从5.45μM到9.05μM。其中，有26种在体外具有最佳的抗肿瘤活性，不仅对正常肿瘤细胞表现出优异的细胞毒性，而且对CDDP耐药细胞系（例如A549 / CDDP和SKOV-3 / CDDP）也表现出优异的细胞毒性。重要的是，26只对HUEVC和LO2等正常细胞系几乎没有影响。此外，以下生物学机制研究表明26种可以有效进入。

A549细胞在G2 / M期显着停止细胞周期，破坏信号传导途径并触发内源性caspase凋亡途径。此外，A549肿瘤的皮下移植模型的结果表明26可以有效地降低肿瘤的生长速度而不会引起体重的减少。