MSI-1436 (Trodusquemine) (Synonyms: Trodusquemine; Aminosterol-1436) |
| رقم الكتالوجGC32396 |
MSI-1436 (ترودوسكيمين) هو مثبط انتقائي غير تنافسي لإنزيم فوسفاتاز التايروزين البروتينية 1B (PTP1B)، بـ IC50 يبلغ حوالي 1 μM، وهو يفضل TCPTP بمعدل 200 مرة (IC50 ،224 μM).
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Cas No.: 186139-09-3
Sample solution is provided at 25 µL, 10mM.
MSI-1436 (Trodusquemine) is a selective non-competitive inhibitor of the enzyme protein tyrosine phosphatase 1B (PTB1B). The IC50 of MSI-1436 is about 1 µM, which is 200 times higher than that of TCPTP (IC50, 224 µM). [1]. Besides,MSI-1436 has antimicrobial activity[6].
Incubation of intact HepG2 cells with 10µM MSI-1436 (Trodusquemine) resulted in a 53% inhibition of phosphatase activity compared with the control (no inhibitor)[1]. MSI-1436 (Trodusquemine) is a "first-in-class" highly selective inhibitor of PTP1B that can cross the blood-brain barrier to suppress feeding and promote insulin sensitivity and glycemic control. in cultured neuronal cells[2]. Selective inhibition of PTP1B in equine ASC EMS cells substantially improved adipogenic differentiation by promoting cellular proliferation and normalizing expression of C/EBPalpha, PPARγ. Levels of secreted adiponectin and PPARγ were also shown to be increased in MSI-1436 (Trodusquemine)-conditioned cells, while total leptin levels markedly dropped under the same conditions[4].
MSI-1436 (Trodusquemine) acts rapidly and leads to significant weight loss after the first dose. A prerequisite for safe and effective antiobesity therapy is to reduce fat without reducing lean muscle mass Trodusquemine-treated mice had no reduction in whole-body protein content, but smaller epididymal fat pads, reduced adipocyte area in white and brown adipose tissue, and significant decrease in whole-body fat composition fat-specific non-cachexic weight loss in MSI-1436 (Trodusquemine) could explain the dependence of percentage weight loss on initial body weight[1]. A single injection of the drug MSI-1436 (Trodusquemine) decreased food intake in rats. To assess the effects of MSI-1436 (Trodusquemine) on DAT function, fast-scan cyclic voltammetry was used to measure DA concentration changes in the ventral striatum. Neither saline nor MSI-1436 (Trodusquemine) caused a significant change in the magnitude of evoked release from baseline values whereas bupropion caused a considerable increase. MSI-1436 (Trodusquemine) is an anti-obesity treatment that spares DAT[5]. MSI-1436 (Trodusquemine) antagonized HER2 signaling, inhibited tumorigenesis in xenografts, and abrogated metastasis in the NDL2 mouse model of breast cancer, validating the inhibition of PTP1B as a therapeutic strategy in breast cancer[7]. The PTP1B inhibitor MSI-1436 (Trodusquemine) normalizes PTP1B activity, restores mGluR5 function, and attenuates the anxiety phenotype in LMO4 KO mice [3].
References:
[1]: Lantz KA, Hart SG, 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):1516-23. doi: 10.1038/oby.2009.444. Epub 2010 Jan 14. PMID: 20075852.
[2]: Qin Z, Pandey NR, 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. doi: 10.1016/j.bbrc.2015.01.040. Epub 2015 Jan 24. PMID: 25623533.
[3]: Qin Z, Zhou X, et,al. Chronic stress induces anxiety via an amygdalar intracellular cascade that impairs endocannabinoid signaling. Neuron. 2015 Mar 18;85(6):1319-31. doi: 10.1016/j.neuron.2015.02.015. Epub 2015 Mar 5. PMID: 25754825.
[4]: Bourebaba L, Kornicka-Garbowska K, et,al.MSI-1436 improves EMS adipose derived progenitor stem cells in the course of adipogenic differentiation through modulation of ER stress, apoptosis, and oxidative stress. Stem Cell Res Ther. 2021 Feb 3;12(1):97. doi: 10.1186/s13287-020-02102-x. PMID: 33536069; PMCID: PMC7860037.
[5]: Roitman MF, Wescott S, et,al. MSI-1436 reduces acute food intake without affecting dopamine transporter activity. Pharmacol Biochem Behav. 2010 Nov;97(1):138-43. doi: 10.1016/j.pbb.2010.05.010. Epub 2010 May 15. PMID: 20478327; PMCID: PMC2945616.
[6]: Shu Y, Jones SR, et,al. The synthesis of spermine analogs of the shark aminosterol squalamine. Steroids. 2002 Mar;67(3-4):291-304. doi: 10.1016/s0039-128x(01)00161-1. PMID: 11856553.
[7]: Krishnan N, Koveal D, et,al.Targeting the disordered C terminus of PTP1B with an allosteric inhibitor. Nat Chem Biol. 2014 Jul;10(7):558-66. doi: 10.1038/nchembio.1528. Epub 2014 May 20. PMID: 24845231; PMCID: PMC4062594.
| Kinase experiment [1]: | |
Preparation Method | Human kinases activities were measured using KINOMEscan. In brief, 256 DNA-tagged kinases, ligand affinity beads, and MSI-1436 (Trodusquemine)(10 µmol/l) were incubated at room temperature, washed, and then eluted. Phage titer in the eluates was quantitated by real-time quantitative PCR. |
Reaction Conditions | 10 µmol/l MSI-1436 (Trodusquemine) |
Applications | Enzyme inhibition assay showed that MSI-1436 (Trodusquemine) inhibited PTP1B 200 times more in a dose-dependent manner than TCPTP (IC 50 = 1 umol/l vs. 224 umol/l). |
| Cell experiment [1]: | |
Cell lines | HepG2 cell line |
Preparation Method | Hep G2 cells were pretreated with 10 µmol/l MSI-1436 (Trodusquemine) or sodium orthovanadate for 10 min at 37°C then incubated with 10 mmol/l pNPP for 30 min at 37 °C Samples of the supernatants were spectrophotometrically analyzed at OD405 for hydolyzed pNP, a direct end product of phosphatase activity. |
Reaction Conditions | 10 µmol/l MSI-1436 (Trodusquemine) for 10 min at 37°C |
Applications | Quantification of phosphatase activity measured in intact cell assays Incubation of intact HepG2 cells with 10 umol/l MSI-1436 (Trodusquemine) resulted in a 53% inhibition of phosphatase activity compared with control (no inhibitor). |
| Animal experiment [1]: | |
Animal models | Male AKR/J mice |
Preparation Method | Male AKR/J mice were randomly placed on ad libitum 10, 45, or 60% fat kcal diets.After 14 weeks, mice were randomly assigned to three treatment groups; MSI-1436 (Trodusquemine), vehicle, or pair-fed. PF animals were injected with saline and allotted the amount of food consumed daily by trodusquemine-treated animals. |
Dosage form | MSI-1436 (Trodusquemine)(initial dose of 10 mg/kg followed by intraperitoneal injection of 5 mg/kg 3 times weekly) for 23 days |
Applications | MSI-1436 (Trodusquemine)-treated animals demonstrated weight loss in a manner proportional to their pretreatment weights; heavier mice lost a greater overall percentage of BW. |
References: | |
| Cas No. | 186139-09-3 | SDF | |
| المرادفات | Trodusquemine; Aminosterol-1436 | ||
| Canonical SMILES | NCCCNCCCCNCCCN[C@@H]1C[C@@](C[C@@H](O)[C@]2([H])[C@]3([H])CC[C@@]4(C)[C@@]2([H])CC[C@@]4([C@H](C)CC[C@@H](OS(=O)(O)=O)C(C)C)[H])([H])[C@]3(C)CC1 | ||
| Formula | C37H72N4O5S | M.Wt | 685.06 |
| الذوبان | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4597 mL | 7.2986 mL | 14.5973 mL |
| 5 mM | 291.9 μL | 1.4597 mL | 2.9195 mL |
| 10 mM | 146 μL | 729.9 μL | 1.4597 mL |
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- Purity: >95.00%
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Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)
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