MSI-1436

MSI-1436 is a selective, non-competitive inhibitor of the enzyme protein-tyrosine phosphatase 1B (PTP1B), with an IC₅₀ of appr 1 μM, 200-fold preference over TCPTP (IC₅₀, 224 μM). IC50 & Target: IC50: 1 μM (PTB1B), 224 μM (TCPTP)^[1] In Vitro: In HepG2, MSI-1436 (10 µM, 30 min) alone has no effect on phosphorylation of IRβ, but in conjunction with 100 nM insulin, MSI-1436 increases p-IRβ 18-fold over untreated cells and by approximately threefold over cells treated with insulin alone. MSI-1436's inhibition of TCPTP is approximately two logs less than the effect on PTP1B activity, with a resulting IC₅₀ value of 224 µM^[1]. MSI-1436 (Trodusquemine, 10 μM) restores ERK phosphorylation in response to mGluR1/5 agonist DHPG in F11 neuronal cells. MSI-1436 (10 uM) rescues DHPG-induced holding currents and restores DSI in LMO4KO BLA neurons^[2]. MSI-1436 (0.1-100 µM) blocks PTP1B activity, has insulin-mimetic effects in cultured neuronal cells^[3]. In Vivo: MSI-1436 (10 mg/kg, i.p.) causes obesity-dependent body weight, reduces total body fat content and adipocyte size and lipid content of white adipose tissue of mice. MSI-1436 treatment significantly reduces plasma insulin levels. MSI-1436 (10 mg/kg, i.p.) increases phosphorylation of STAT-3 2.7-fold and, in conjunction with 100 U/kg insulin, p-IRβ increases threefold over insulin alone-treated rats^[1]. MSI-1436 (Trodusquemine) exhibits anxiolytic effect through a restoration of endocannabinoid (eCB) signaling within the amygdala^[2]. MSI-1436 (5 mg/kg, i.p.) has an anti-diabetic effect on diabetic mice, and is sufficient to suppress food intake and cause weight loss in CD1 mice^[3].