Menin与MLL1 (KMT2A) n端Menin结合域(MBD)结合。 01 研究背景 Menin 抑制剂 (MI) 单药治疗(例如 SNDX-5613)可诱导携带 MLL1-r 或 mtNPM1 的复发/难治性 AML 患者的临床缓解,但大多数患者要么无反应,要么最终复发。利用单细胞 RNA-Seq、ChiP-Seq、ATAC-Seq、RNA-Seq、RPPA 和质谱细胞术 (CyTOF) 分...
Meanwhile, recent studies found that menin–MLL1 interaction inhibitors exhibited a firm tumor suppressive ability in specific cancer cells, such as prostate cancer, breast cancer, liver cancer, and lung cancer. Overall, it seems to serve as a novel therapeutic means for cancers....
Therefore, targeting the menin–MLL1 protein–protein interface represents a promising strategy to block MLL-mediated leukemogenesis. On the basis of co-crystal structure analysis, starting from thienopyrimidine chemotype, we have investigated the detailed structure–activity relationship of the piperazinyl...
Inhibition of COMPASS complex by blocking the Menin-MLL1 interaction is reported to be effective in different cancers. In this study, we found that a specific Menin-MLL1 inhibitor, MI-503 inhibits neuroblastoma cancer stem cells (NB CSCs; CD114+ cells) to inhibit overall neuroblastoma (NB) ...
We hypothesized that Menin-MLL1 inhibition will inhibit neuroblastoma cancer stem cells (NB CSCs; CD114+ cells) to inhibit overall neuroblastoma (NB) growth. NB is an extracranial solid pediatric cancer that accounts for 10-15% of all pediatric cancer-related deaths, with the long-term ...
Conclusion: We have generated a novel, potent, orally available small-molecule inhibitor of the Menin-MLL1 interaction, DS-1594a. Our results suggest that DS-1594a has medicinal properties distinct from those of cytarabine and that DS-1594a has the potential to be a new anticancer therapy ...
Abstract 3841: Therapeutic targeting of FLT3 mutations in AML via menin-MLL1 and FLT3 inhibitiondoi:10.1158/1538-7445.AM2019-3841Acute myeloid leukemias (AML) that are driven by MLL1 (KMT2A)-fusion proteins (MLL-f) or NPM1 mutations (NPM1mut) are both associated with aberrant expression ...
However, wild-type MLL1 plays a critical role in sustaining hematopoietic stem cells (HSCs), thus the disruption of the Menin-MLL1 interaction would be expected to ablate normal hematopoiesis. We set out to address the importance of the Menin-MLL1 interaction during normal hematopoiesis, ...
Inhibition of MLL1‐menin interaction attenuates renal fibrosis in obstructive nephropathydoi:10.1096/fj.202100634RRRZou, JiananYu, ChaoZhang, ChunyunGuan, YingjieZhang, YunheTolbert, EvelynZhang, WeiZhao, TingBayliss, GeorgeLi, XiaogangFASEB Journal...
Svoboda LK, Bailey N, Van Noord RA, et al. Tumorigenicity of Ewing sarcoma is critically dependent on the trithorax proteins MLL1 and menin. Oncotarget. 2017;8(1):458-471.Svoboda LK, Bailey N, Van Noord RA, Krook MA, Harris A, Cramer C, et al. Tumorigenicity of Ewing sarcoma is ...