Uses
O-304 is a first-in-class, orally available pan-AMPK activator, which increases AMPK activity by suppressing the dephosphorylation of pAMPK. O-304 exhibits a great potential as a agent to treat type 2 diabetes (T2D) and associated cardiovascular complications [1][2].
Mechanism of action
O-304 acts as an AMPK-specific activator to treat testosterone propionate-induced benign prostatic hyperplasia (BPH) in rats via oral administration[3]. Its mechanism of action involves the specific activation of AMPK, which in turn activates the downstream PGC-1α signalling pathway, thereby inhibiting inflammation, proliferation and mitochondrial dysfunction associated with the progression of BPH, and thus exerting a potential therapeutic effect on BPH.
in vivo
O-304 increases glucose uptake in skeletal muscle, reduces β cell stress, and promotes β cell rest in diet-induced obese mice. O-304 reduces fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin[2].
References
[1] Periodic Reporting for period 1-AMPK-DIAB (A small molecule AMP activated protein kinase (AMPK) activator, denoted O304, as a novelinnovative drug for the treatment of type 2 diabetes).
[3] Yongzhi Li. (2021). SIRT3 affects mitochondrial metabolic reprogramming via the AMPK-PGC-1α axis in the development of benign prostatic hyperplasia. Prostate, 81 15, 1135–1148.
https://doi.org/10.1002/pros.24208
