A26-A6 is a MTDH-SND1 interaction blocker (IC50 = 2.4 μM by cell-free & 12.3 μM by cellular split-luc assay) that competes against metadherin (MTDH; AEG-1; LYRIC) for staphylococcal nuclease domain-containing 1 (SND1) binding, thereby preventing MTDH-SND1 complex from suppressing antitumor T cell responses. A26-A6 inhibits PyMT tumor sphere formation in cultures (IC50 <200 μM) in a MTDH- and SND1-dependent manner and exhibits in vivo efficacy against breast tumor growth and metastasis in mice in vivo (15 mg/kg/d i.v. 5d/wk), including the murine PyMT model, and human breast cancer xenografts (PDX, HCI-001, SCP28).
Metadherin-staphylococcal nuclease domain-containing 1 (MTDH-SND1) interaction inhibitor with anti-triple-negative breast cancer (TNBC) efficacy in vivo.
Metastatic 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
Despite increased overall survival rates, curative options for metastatic breast cancer remain limited. We have previously shown that metadherin (MTDH) is frequently overexpressed in poor prognosis breast cancer, where it promotes metastasis and therapy resistance through its interaction with staphylococcal
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