trodusquemine
A naturally-occurring cholestane and non-competitive, allosteric inhibitor of protein tyrosine phosphatase 1B (PTP1B), with potential hypoglycemic, anti-diabetic, anti-obesity, and antineoplastic activities. Upon administration, trodusquemine selectively targets and inhibits PTP1B, thereby preventing PTP1B-mediated signaling. This prevents the dephosphorylation of the insulin receptor, which improves insulin signaling and insulin sensitivity, and decreases blood glucose levels. In susceptible cancer cells, inhibition of PTP1B causes a reduction of tumor cell proliferation. In addition, as trodusquemine can cross the blood-brain barrier (BBB), it centrally suppresses appetite and causes weight loss. PTP1B, a tyrosine phosphatase, is elevated in certain cancer cells; it is specifically upregulated in human epidermal growth factor receptor 2 (HER2)-driven cancers where it promotes cell growth, and is correlated with a poor prognosis and increased metastatic potential. In diabetes, PTP1B upregulation plays a major role in insulin resistance.
Synonym: | MSI-1436 |
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Code name: | MSI-1436C |
Chemical structure: | (24R)-3beta-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-7alpha-hydroxy-5alpha-cholestan-24-yl hydrogen sulfate cholestane-7,24-diol, 3-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-, 24-(hydrogen sulfate), (3beta,5alpha,7alpha,24R)- |