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.

The small molecule PF-429242 was developed as a hypolipidemic agent based on high throughput screening in a Pfizer compound library. PF-429242 is a competitive inhibitor of sterol regulatory element-binding protein (SREBP) site 1 protease (IC50 = 0.175 uM). It is selective for site 1 protease against a panel of serine proteases. PF-429242 inhibits rate of cholesterol synthesis in CHO cells (IC50 = 0.53 uM). PF-429242 inhibits the activity of S1P reversibly and competitively and suppresses the expression level of SREBP target genes, consequently decreasing cellular lipid levels. It has been shown that PF-429242 suppresses hepatic SREBP target genes and inhibits cholesterol and fatty acid synthesis in a mouse model. It also has been reported that PF-429242 suppresses viral replication in cells infected with hepatitis C virus (HCV), Lassa virus, lymphocytic choriomeningitis virus, New World arenaviruses and Dengue virus.

BMS-687453 is a potent and selective PPARα agonist, with an EC50 of 10 nM for human PPARα and 410-fold selectivity vs human PPARγ in PPAR-GAL4 transactivation assays.

BMS-309403, a substance used as an inhibitor of adipocyte fatty acid-binding protein, has been suggested as a new therapeutic agent for treating type 2 diabetes mellitus and atherosclerosis. Fatty acid binding proteins (FABPs) are small-molecular weight hydrophobic proteins containing a large hydrophobic cavity, into which naturally occurring long-chain fatty acids and synthetic hydrophobic ligands can be accepted. FABPs act as transporters of endogenous fatty acids from the cell surface to various sites of fatty acid storage and metabolism. In addition to the roles of FABP4 in regulating lipid metabolism and insulin sensitivity, recent pharmacological and biological findings have indicated a regulatory function of FABP4 in inflammation. FABP4 is expressed mainly to macrophages and inflammatory response. BMS-309403 competes with fatty acids for the binding pocket of A-FABP with high specificity. BMS-309403 is regarded as a lead compound for effective treatment of obesity related cardio-metabolic diseases. It also has off-target activity - it stimulates glucose uptake in C2C12 myotubes in a temporal and dose dependent manner via activation of AMP-activated protein kinase (AMPK) signaling pathway but independent of FABPs

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.