12:00 AM
Aug 15, 2016
 |  BioCentury  |  Emerging Company Profile

Restraining translation

Bantam's eIF4E inhibitors disrupt oncogene translation and cancer metabolism

Bantam Pharmaceutical LLC is developing small molecule eukaryotic translation initiation factor 4E inhibitors that selectively inhibit translation of several tumor-promoting genes and disrupt cancer cell metabolism. It hopes to show the mechanism of its lead compound will lead to a therapeutic more potent or safer than competing compounds in the same pathway.

mRNA translation begins with binding of a ribosome to the 5' end of an mRNA. This is facilitated by eukaryotic initiation factors including the eukaryotic translation initiation factor 4F (eIF4F) complex, which comprises three subunits: eIF4E cap-binding protein, eIF4G scaffolding protein and eIF4A RNA helicase. According to Bantam CEO Michael Luther, eIF4E is the rate-limiting subunit of the eIF4F complex.

mRNAs with long 5' untranslated regions (UTRs) rely more heavily on eIF4E to initiate translation compared to mRNAs with short 5' UTRs.

Luther said the majority of mRNAs with long 5' UTRs code for oncogenes including cyclin D1 (CCND1; BCL1), VEGF, v-myc myelocytomatosis viral oncogene homolog (MYC; c-Myc) and ornithine decarboxylase (ODC). By contrast, mRNAs with...

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