H3B-8800
未知生产厂商
H3B-8800 is a novel spliceosome inhibitor developed by H3 Biomedicine . It offers the benefit of preferentially killing spliceosome-mutant cancer cells whereas other splicesome inhibitors, such as the pladienolide analogue E7107, show no such preferential targeting . H3B-8800 was granted orphan drug status by the FDA in August 2017 and is in clinical trials for the treatment of acute myelogenous leukemia and chronic myelomonocytic leukemia .
H3B-8800 is a novel spliceosome inhibitor developed by H3 Biomedicine . It offers the benefit of preferentially killing spliceosome-mutant cancer cells whereas other splicesome inhibitors, such as the pladienolide analogue E7107, show no such preferential targeting . H3B-8800 was granted orphan drug status by the FDA in August 2017 and is in clinical trials for the treatment of acute myelogenous leukemia and chronic myelomonocytic leukemia .
H3B-8800 is thought to bind to a site similar to pladienolides on the SF3B complex within the spliceosome . Once bound it induces increased retention of short (<300 nucleotide) GC-rich introns through modulation of pre-mRNA processing. These intron-retained mRNA sequences are then thought to be destroyed through the nonsense-mediated decay pathway. It has been suggested that modulation by H3B-8800 is mediated by disruption of branchpoint sequence recognition by the SF3B complex as there is overall less preference for adenosine as the branchpoint nucleotide and a greater amount of sequences with weaker association to the SFB3 in introns retained with H3B-8800. It was found that 41 of 404 genes encoding spliceosome proteins contained GC-rich sequences whose retention was induced by H3B-8800 . It is suggested that this is key to the specificity of H3B-8800's lethality as cells with spliceosome-mutant cells are dependent on the expression of wild-type spliceosome components for survival . Since cancer cells, as in myelodysplasia, experience SF3B1 mutations much more frequently than host cells, this allows H3B-8800 to be used to preferentially target these cells by inducing intron-retention in critical spliceosome component pre-mRNA leading to destruction of the now nonsense mature RNA ultimately cell-death due to the lack of these critical proteins .
每项发明一条，涵盖美国、欧洲、PCT 与中国的同族专利。
未检索到以该名称命名的专利
专利文献通常使用化学名或研发代号指代药物，而非通用名；且专利申请在提交约 18 个月后才公开，较新的药物可能尚未出现在这里。
