抑制癌细胞中特定靶点，减轻不良副作用已经成为胰腺癌治疗的一种有前途的策略。MAP4K4与胰腺癌的发展有关并且与不良的临床结果相关联。通过磷酸化MKK4，与细胞凋亡和生存相关的蛋白被转化。因此，在胰腺肿瘤中抑制MAP4K4的活性是一种新的治疗策略。因此，我们进行了基于结构的虚拟筛选，以发现MAP4K4抑制剂，并发现化合物F389-0746具有强力抑制作用(IC50为120.7 nM)。激酶分析结果显示，F389-0746对MAP4K4高度选择性，不太可能引起副作用。体外实验结果显示，F389-0746显著抑制了癌细胞的生长和存活。体内实验结果显示，F389-0746的肿瘤抑制效果与接受吉西他滨治疗的组别相当。这些发现表明，F389-0746具有很好的潜力，可以进一步作为新型胰腺癌治疗药物的开发。

Inhibiting a specific target in cancer cells and reducing unwanted side effects has become a promising strategy in pancreatic cancer treatment. MAP4K4 is associated with pancreatic cancer development and correlates with poor clinical outcomes. By phosphorylating MKK4, proteins associated with cell apoptosis and survival are translated. Therefore, inhibiting MAP4K4 activity in pancreatic tumours is a new therapeutic strategy. Herein, we performed a structure-based virtual screening to identify MAP4K4 inhibitors and discovered the compound F389-0746 with a potent inhibition (IC50 120.7 nM). The results of kinase profiling revealed that F389-0746 was highly selective to MAP4K4 and less likely to cause side effects. Results of in vitro experiments showed that F389-0746 significantly suppressed cancer cell growth and viability. Results of in vivo experiments showed that F389-0746 displayed comparable tumour growth inhibition with the group treated with gemcitabine. These findings suggest that F389-0746 has promising potential to be further developed as a novel pancreatic cancer treatment.