St. Jude Reference #SJ-20-0033
Researchers at St. Jude discovered a first-in-class small molecule inhibitor of Melanoma-associated antigen (MAGE) for the treatment of various cancers including lung, ovarian, and medulloblastoma. The inhibitor prevents MAGE-A11 ubiquitin ligase from binding to its substrate, PCF11. MAGE-A11 is normally restricted to expression in reproductive tissues (e.g. testis), but is aberrantly expressed in many tumors. It has been shown that MAGE-A11 acts as an oncogene, and depletion of MAGE-A11 slows cancer cell growth and tumor formation in vivo. Consequently, the discovery of MAGE-A11 inhibitors could have commercial applications as cancer-specific therapeutics.
Most cancer therapeutics are non-cancer specific with detrimental side effects, and no therapeutics are directedly inhibiting MAGE proteins. Thus, MAGE-directed therapeutics may have advantage due to its relatively restricted expression pattern. Our discovery may lead to the development of first-in-class cancer retreatments.
small molecule inhibitor, Melanoma-associated antigen (MAGE), cancer, lung, ovarian, medulloblastoma, MAGE-A11 ubiquitin ligase, PCF11 substrate, E3 ligase, protein degradation
Granted patents or published applications
Provisional application pending.
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