2:58 PM
Nov 30, 2017
 |  BC Innovations  |  Translation in Brief

Two faces of FOXO1

Columbia and AZ create new class of FOXO1 inhibitor

Columbia University and AstraZeneca plc (LSE:AZN; NYSE:AZN) have identified the first FOXO1 inhibitors that can selectively block the transcription factor’s glucose-stimulating activity without inducing lipogenesis. Optimization of the compounds could yield a therapy for Type II diabetes that avoids the weight gain and cardiovascular effects of marketed drugs.

Insulin sensitizers such as the generic drug metformin help keep blood glucose levels in check, but because of insulin’s dual role in the liver they also trigger lipogenesis. Both those effects result from insulin’s inhibition of forkhead box O1 (FOXO1).

The transcription factor boosts glucose production by triggering expression of glucose-6-phosphatase catalytic subunit-related protein (G6PC; G6Pase) and inhibits glucose utilization and lipogenesis...

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