异柠檬酸脱氢酶突变体抑制剂在神经胶质瘤治疗中的研究进展

Research progress on mutant isocitrate dehydrogenase inhibitors in treatment of glioma

异柠檬酸脱氢酶(IDH)1和2是细胞代谢的关键酶,参与多个生理过程。IDH突变(mIDH)在肿瘤发展中起关键或决定性作用,是胶质瘤药物开发的重要靶点。制药企业不断开发针对mIDH的抑制剂,Ivosidenib和Enasidenib已被FDA批准用于治疗复发难治性急性髓细胞性白血病(AML),并进一步开展针对胶质瘤的试验;Olutasidenib,Vorasidenib,NOA-16等正在进行Ⅰ/Ⅱ期临床试验;AGI-5198,GSK-321等止步于临床前研究。对这些小分子抑制剂和疫苗的临床前研究成果及临床试验进展进行总结,以期为胶质瘤药物开发提供参考。

Isocitrate dehydrogenase(IDH) 1 and 2 are key enzymes in cell metabolism,which participate in multiple physiological processes.Mutant IDHs(mIDH) play a key or decisive role in tumor development and have become a kind of important targets for glioma drug.Pharmaceutical companies continue to develop inhibitors against mIDH.Ivosidenib and Enasidenib have been approved by the FDA for the treatment of relapsed or refractory acute myeloid leukemia(AML), which are continued to be studied in trials in glioma;Olutasidenib, Vorasidenib, NOA-16 and some other inhibitors are under phase Ⅰ/Ⅱ clinical trials;AGI-5198, GSK-321, etc.have stopped in preclinical research.In this review, we summarize the preclinical research results and clinical trial progress of some small molecule inhibitors and vaccines, hoping to provide a reference for the development of glioma drugs.