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ENT-03 is a novel, centrally acting endogenous aminosterol (specifically, a spermine-bile acid conjugate) developed by Enterin for the treatment of obesity and type 2 diabetes. It acts as an inhibitor of protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of insulin and leptin signaling. By inhibiting PTP1B, ENT-03 enhances insulin sensitivity, normalizes blood glucose levels independently of weight loss, reduces food intake, promotes sustained weight loss, eliminates liver fat, and improves liver function in preclinical models. The drug exerts its effects primarily through central nervous system circuits involved in energy homeostasis and metabolism regulation. Unlike GLP‑1 agonists such as semaglutide—which act peripherally—ENT‑03 targets hypothalamic pathways with distinct neural circuit engagement[4][5][6][7][10]. Phase 1 clinical trials are ongoing for obesity and type 2 diabetes.
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