这两类药物均对PRMT5具有强抑制活性,显示了强抗肿瘤活性,但由于对正常细胞和肿瘤细胞的PRMT5均具有强抑制活性,因此观测到了很强的血液毒性,限制了其临床应用,从而影响了其临床治疗效果。 2016年,发表在Science上的论文揭示了MTAP缺失与PRMT5具有合成致死作用 (Science .2016 Mar 11;351(6278):1214‑8.)。MTAP...
9. Mavrakis KJ, McDonald ER, 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, et al. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science. 2016;351(6278):1208-13. $和誉-B(02256)$...
mtap缺失会导致甲基硫腺苷(mta)的积累,它与sam具有相似的结构,并通过改变mta和sam的比例使细胞对prmt5抑制敏感(kryukov et al.science 2016,351(6278),1218)。升高的mta会选择性地与sam竞争结合prmt5,并能部分抑制prmt5的甲基化活性,从而降低整个蛋白质组的对称精氨酸二甲基化水平,提高细胞对调节甲基小体活性的...
本发明提供了一种化合物作为PRMT5‑MTA抑制剂,其为式(I)所示化合物或其药学上可接受的盐、同位素变体、互变异构体、立体异构体、前药、多晶型、水合物或溶剂合物。本发明还提供了包含所述化合物的药物组合物,及其在治疗癌症中的用途。 (19)国家知识产权局 (12)发明专利申请 (10)申请公布号 CN 116178347 ...
Here, we report that PRMT5 physically associates with the transcription factor Snail and the NuRD(MTA1) complex to form a transcriptional-repressiv... J Gao,R Liu,D Feng,... - Springer Science and Business Media LLC 被引量: 0发表: 2021年 加载更多...
A review of the known MTA-cooperative PRMT5 inhibitorsProtein arginine methyltransferase 5 (PRMT5), an epigenetic target with significant clinical potential, is closely associated with the occurrence and development of a range of tumours and has attracted considerable interest from the pharmaceutical ...
9. Mavrakis KJ, McDonald ER, 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, et al. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science. 2016;351(6278):1208-13. (和誉-B)
9. Mavrakis KJ, McDonald ER, 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, et al. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science. 2016;351(6278):1208-13.
9. Mavrakis KJ, McDonald ER, 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, et al. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5. Science. 2016;351(6278):1208-13. (和誉-B)
9. Mavrakis KJ, McDonald ER, 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, et al. Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5.Science.2016;351(6278):1208-13.