Trodusquemine (MSI-1436) is a "first-in-class" highly selective non-competitive, allosteric inhibitor of PTP1B that can cross the blood-brain barrier to suppress feeding and promote insulin sensitivity and glycemic control. Trodusquemine is a naturally occurring cholestane that can be purified from the liver of the dogfish shark, Squalus acanthias, but it can also be manufactured synthetically by a fairly laborious process that requires several weeks. Trodusquemine has 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.

A-769662 stimulates partially purified rat liver AMPK with EC50 with 0.8 uM. A-769662 activates AMPK purified from multiple tissues and species in a dose-responsive manner with modest variations in observed EC50s. EC50s determined for A-769662 using partially purified AMPK extracts from rat heart, rat muscle, or human embryonic kidney cells (HEKs) are 2.2 uM, 1.9 uM, or 1.1 uM, respectively. A 4 hours treatment of primary rat hepatocytes with A-769662 dose-dependently increases ACC phosphorylation, which correlated inhibition of fatty acid synthesis with IC50 of 3.2 uM. A-769662 also inhibits fatty acid sythesis in mouse hepatocytes with IC50 with 3.6 uM. A-769662 activates AMPK both allosterically and by inhibiting dephosphorylation of AMPK on Thr-172, similar to the effects of AMP. A-769662 inhibits proteasomal function by an AMPK-independent mechanism. A-769662 affects the in vitro activity of purified 26S proteasomes but not the in vitro activity of purified 20S proteasomes. A-769662 has toxic effects on MEF cells. A recent research shows A-769662 inhibited cell proliferation and DNA synthesis.

Trodusquemine (MSI-1436) is a "first-in-class" highly selective non-competitive, allosteric inhibitor of PTP1B that can cross the blood-brain barrier to suppress feeding and promote insulin sensitivity and glycemic control. Trodusquemine is a naturally occurring cholestane that can be purified from the liver of the dogfish shark, Squalus acanthias, but it can also be manufactured synthetically by a fairly laborious process that requires several weeks. Trodusquemine has 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.