7knw
Crystal structure of SND1 in complex with C-26-A2
Structural highlights
FunctionSND1_HUMAN Functions as a bridging factor between STAT6 and the basal transcription factor. Plays a role in PIM1 regulation of MYB activity. Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2).[1] Publication Abstract from PubMedMetastatic breast cancer is a leading health burden worldwide. Previous studies have shown that metadherin (MTDH) promotes breast cancer initiation, metastasis and therapy resistance; however, the therapeutic potential of targeting MTDH remains largely unexplored. Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors. We performed a small-molecule compound screening to identify a class of specific inhibitors that disrupts the protein-protein interaction (PPI) between MTDH and SND1 and show that our lead candidate compounds C26-A2 and C26-A6 suppressed tumor growth and metastasis and enhanced chemotherapy sensitivity in preclinical models of triple-negative breast cancer (TNBC). Our results demonstrate a significant therapeutic potential in targeting the MTDH-SND1 complex and identify a new class of therapeutic agents for metastatic breast cancer. Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis.,Shen M, Wei Y, Kim H, Wan L, Jiang YZ, Hang X, Raba M, Remiszewski S, Rowicki M, Wu CG, Wu S, Zhang L, Lu X, Yuan M, Smith HA, Zheng A, Bertino J, Jin JF, Xing Y, Shao ZM, Kang Y Nat Cancer. 2022 Jan;3(1):43-59. doi: 10.1038/s43018-021-00279-5. Epub 2021 Nov, 29. PMID:35121987[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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