AKB-4924 is a small molecule that stabilizes hypoxia inducible factor-1α (HIF-1α). HIF-1α is critical for the regulation of innate immune responses and maintenance of epithelial barrier function in the gastrointestinal tract. We are developing AKB-4924 as a once-daily, orally-administered treatment option for inflammatory bowel disease.
How AKB-4924 Works
The response to hypoxia (reduced oxygen) is a critical mechanism by which cells regulate metabolism, immune function, and many other adaptive responses. Hypoxia-inducible factor (HIF) is the primary transcriptional regulator of this response. Amongst its many properties, HIF-1α is a critical regulator of epithelial barrier function and the innate immune response. Stabilization of HIF-1α has been shown to dramatically improve wound healing and immune response in the gut. AKB-4924 is a novel small molecule that stabilizes cellular levels of HIF-1α by inhibiting prolyl hydroxylase enzymes, the primary enzymes responsible for the destruction of HIF-1α.
AKB-4924 is being developed for inflammatory bowel disease (IBD). It has shown outstanding efficacy for induction and maintenance in multiple models of inflammatory bowel disease. By stabilizing HIF-1α, AKB-4924 greatly reduces the severity of colitis as measured by reduction in clinical symptoms, restoration of colon length, and preservation of the barrier function. Our Phase 1b trial will treat patients with ulcerative colitis.
Publications about AKB-4924
HIF prolyl hydroxylase inhibition reverses disease symptoms in established TNBS colitis.Read the abstract.