Molecular Targets for the Anti-cancer Natural Product Pateamine A

v The natural marine product Pateamine A (PatA) is a potent anti-tumor and pro-apoptotic agent. Until recently, PatA?s mechanism of action was unknown until scientists at JHU determined that the protein inhibits cell proliferation through blockade of eukaryotic translation initiation. Specifically, PatA binds to and enhances the activity of eIF4A and causes changes in the affinity of eIF4A for its partner proteins, resulting in the stalling of initiator complexes on mRNA in vitro. In addition to its property as a novel anti-tumor agent, PatA is also an effective immunosuppressant that inhibits an intracellular signal transduction cascade that culminates in the transcription of cytokines such as IL-2. In a structure/activity study, a structurally simplified analog of pateamine, des-methyl, des-amino pateamine (DMDA-PatA), was synthesized and found to retain the anti-tumor and immunosuppressive activity of the less accessible parent natural product. Description (Set) Proposed Use (Set) PatA and its novel analogs are good candidates for further evaluation as anticancer and immunosuppressant drugs. The molecular targets identified for PatA within the translation initiation process can be exploited for screening similar small molecular inhibitors. PatA and its novel analogs may be used to develop drugs for treatment of systemic autoimmune diseases such as lupus erythematosus and diabetes.

Inventor(s): Liu, Jun

Type of Offer: Licensing

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