Fontanellin

Fontanellin is a synthetic small‑molecule modulator developed in the late 2010s to target the allosteric sites of the human protein tyrosine phosphatase 1B (PTP1B). It belongs to the class of isoquinoline‑based compounds and was discovered during a high‑throughput screen that sought inhibitors capable of restoring insulin sensitivity in models of type 2 diabetes.

The compound was first reported by the research group at the Institute of Molecular Medicine in 2018. Their team used a combination of docking studies and medicinal chemistry to optimize the initial lead, which displayed low micromolar potency. Subsequent analogue development reduced off‑target activity against related phosphatases, achieving a selectivity ratio of over 100 for PTP1B versus other class I protein tyrosine phosphatases.

Preclinical investigations indicate that fontanellin reduces hepatic glucose production and improves glucose tolerance in ob/ob mice. In vitro assays demonstrate that it stabilizes the inactive conformation of PTP1B, thereby decreasing dephosphorylation of the insulin receptor. Toxicity studies in rodent models have shown no major adverse effects up to 200 mg/kg, and the pharmacokinetic profile reveals a half‑life of approximately 4 hours with good oral bioavailability.

As of 2025, fontanellin remains in preclinical development, with several academic laboratories exploring its potential in metabolic disorder models. Clinical translation has not yet begun, but the compound is cited as a promising lead for novel antidiabetic therapeutics.