<Suppliers Price>

MSI-1436

Names

[ CAS No. ]:
186139-09-3

[ Name ]:
MSI-1436

[Synonym ]:
KKC12PIF16
MSI-1436
Cholestane-7,24-diol, 3-[[3-[[4-[(3-aminopropyl)amino]butyl]amino]propyl]amino]-, 24-(hydrogen sulfate), (3β,5α,7α,24R)-
trodusquemine
(3β,5α,7α,24R)-3-{[3-({4-[(3-Aminopropyl)amino]butyl}amino)propyl]amino}-7-hydroxycholestan-24-yl hydrogen sulfate

Biological Activity

[Description]:

MSI-1436 is a selective, non-competitive inhibitor of the enzyme protein tyrosine phosphatase 1B (PTB-1B), with an IC50 of appr 1 μM, 200-fold preference over TC-PTP (IC50, 224 μM).

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase
Research Areas >> Endocrinology

[Target]

IC50: 1 μM (PTB-1B), 224 μM (TC-PTP)[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].

[Animal admin]

Mice Male AKR/J mice are randomLy placed on ad libitum 10, 45, or 60% fat kcal diets. After -14 weeks, mice are randomly assigned to three treatment groups (n=5-8 mice/group); MSI-1436 (initial dose of 10 mg/kg with three subsequent weekly doses of 5 mg/kg, intraperitoneally), vehicle (saline, 10 mL/kg, weekly 4×), or pair-fed (PF). PF animals are injected with saline (weekly 4×) and allotted the amount of food consumed daily by MSI-1436-treated animals. On day 23, mice are anesthetized and euthanized for blood and tissue collection, respectively. Plasma is obtained following centrifugation of blood 14,000 rpm for 10 min at 4°C. Rats Nine-week-old male Sprague-Dawley rats (225-260 g) with ad libitum access to normal rodent chow are dosed intraperitoneally with MSI-1436 (10 mg/kg, IP) or saline. After an overnight fast, the rats are dosed intraperitoneally with saline or 100 U/kg of insulin. At 30 min after dose, animals are killed, and hypothalami are harvested and homogenized in 1 mL of tissue extraction reagent plus phosphatase and protease inhibitors. Samples are centrifuged (14,000 rpm for 10 min at 4°C), and the protein content of the supernatants are quantitated via BCA kit.

[References]

[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.

[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.

[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.


[Related Small Molecules]

SHP099 hydrochloride | LB-100 | Salubrinal | Calyculin A | SF1670 | Stibogluconate sodium | TPI-1 | MSI-1436 lactate | Microcystin-LR | Sodium orthovanadate | GSK 2830371 | PTP1B-IN-2 | Rosiptor | NSC 663284(DA3003-1) | TCS 401

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Molecular Formula ]:
C37H72N4O5S

[ Molecular Weight ]:
685.056

[ Exact Mass ]:
684.522339

[ LogP ]:
6.24

[ Index of Refraction ]:
1.548

[ Storage condition ]:
2-8℃


Related Compounds