OCR7575: A novel enzymatic target for metabolic disease/obesity

Fundamental Insulin/GLUT4

• Biology:
  • Insulin stimulates the proteolytic cleavage of TUG to translocate GLUT4 transporters and to promote glucose uptake (A). TUG-C, the C-terminal cleavage product of TUG, translocates into the nucleus (B), and modulates metabolic activity via interaction with PPARg and PGC-1a.
• Validity of Clinical Hypothesis:
  • Human: SNP in PPARg modulates TUG-C binding/PPARg activity
• In vivo Validation:
  • Mouse: TUG-C regulates energy expenditure. GOF = “TUG-C Preservation” increased energy expenditure (C).
  • Mouse: In vivo validation of OCR7575 as a target (D).