MSI-1436 是具有选择性的 PTP1B 的非竞争性抑制

MSI-1436  (Synonyms: Trodusquemine; Aminosterol-1436)

MSI-1436 是具有选择性的 PTP1B 的非竞争性抑制剂，其 IC₅₀ 为 1 μM，而对 TCPTP 的 IC₅₀ 值为 224 μM。

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生物活性    
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)

体外研究
(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

体内研究
(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

分子量    
685.06

性状    
Solid

Formula    
C37H72N4O5S

CAS 号    
186139-09-3

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
 

参考文献

[1]. Lantz KA, et al. Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring). 2010 Aug;18(8):1516-1523.  [Content Brief] [2]. Qin Z, et al. Chronic stress induces anxiety via an amygdalar intracellular cascade that impairs endocannabinoid signaling. Neuron. 2015 Mar 18;85(6):1319-31.  [Content Brief] [3]. Qin Z, et al. Functional properties of Claramine: a novel PTP1B inhibitor and insulin-mimetic compound. Biochem Biophys Res Commun. 2015 Feb 27;458(1):21-7.  [Content Brief]