Publications by authors named "Beth Fernandez"
The uniqueness in each person's cancer cells and variation in immune infiltrates means that each tumor represents a unique problem, but therapeutic targets can be found among their shared features. Radiation therapy alters the interaction between the cancer cells and the stroma through release of innate adjuvants. The extranuclear DNA that can result from radiation damage of cells can result in production of the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) by cyclic GMP-AMP synthase (cGAS).
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- * The oligosaccharyltransferase (OST) complex, particularly the STT3A/B enzymes, plays a crucial role in this glycosylation and has emerged as a promising target for broad-spectrum antiviral drugs.
- * The study highlights the balance between the antiviral potential of STT3A/B inhibitors, like NGI-1, and the need to assess their safety for humans, leading to the discovery of improved compounds that ensure both efficacy and lower toxicity risks.
Dimethyl fumarate is approved for the treatment of multiple sclerosis but is also associated with off-target activation of the niacin receptor. By using a tetrazolone or triazolone bioisostere approach to the fumarate and vinyl sulfone series of Nrf2 activators, we have optimized the electrophilicity of the double bond to tune the on-target Nrf2 activation with PK properties to achieve efficacy in animal models of multiple sclerosis. The study linked highly potent, highly electrophilic molecules to low plasma stability and, subsequently, limited efficacy.
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