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| Targets |
JTT 551 primarily targets protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of insulin signaling. PTP1B dephosphorylates the insulin receptor and its downstream signaling molecules, thereby attenuating insulin signal transduction. By inhibiting PTP1B, JTT 551 enhances insulin signaling and promotes glucose uptake, making it a potential therapeutic agent for type 2 diabetes mellitus. JTT 551 also inhibits TCPTP (T-cell protein tyrosine phosphatase) with a Ki of 9.3 microM, showing approximately 42-fold selectivity for PTP1B over TCPTP. This selectivity is important for minimizing off-target effects, as TCPTP is involved in immune function. Through its inhibition of PTP1B, JTT 551 affects multiple signaling pathways involved in metabolism and insulin sensitivity.
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| ln Vitro |
JTT 551 is a protein tyrosine phosphatase 1B (PTP1B) selective inhibitor. Its Kis values for PTP1B and TCPTP (T-cell protein tyrosine phosphatase) are 0.22 μM and 9.3 μM, respectively. Leukocyte common antigen-related (LAR) PTP and CD45 PTP (CD45) show low affinity for JTT 551, with Kis > 30 μM for each. Moreover, JTT-551 (10 and 30 μM) improves the dose-dependent deoxyglucose uptake induced by insulin [1].
JTT 551 demonstrates potent and selective in vitro inhibitory activity against PTP1B with a Ki of 0.22 microM. The compound also inhibits TCPTP with a Ki of 9.3 microM, showing approximately 42-fold selectivity for PTP1B over TCPTP. This selectivity makes JTT 551 a valuable tool for studying the role of PTP1B in insulin signaling and metabolic regulation without significant interference from TCPTP. The compound's potent inhibition of PTP1B enhances insulin receptor phosphorylation and downstream signaling, promoting glucose uptake and improving insulin sensitivity. JTT 551 can be used in the research of type 2 diabetes mellitus. The compound has a molecular weight of 605.85 and a molecular formula of C34H43N3O3S2. |
| ln Vivo |
JTT 551 (3 mg/kg, 30 mg/kg, orally) dose-dependently decreases blood glucose levels in db/db mice on days 7, 14, and 28. JTT 551 also significantly lowered triglyceride (TG) levels at a dose of 30 mg/kg on day 7 without changing insulin and total cholesterol (TC) levels [1].
JTT 551 has demonstrated in vivo activity as a PTP1B inhibitor in research models of type 2 diabetes mellitus. As a selective small-molecule inhibitor of PTP1B, JTT 551 enhances insulin signaling by preventing the dephosphorylation of the insulin receptor and its downstream signaling molecules. The compound's in vivo effects include improved insulin sensitivity and glucose tolerance in animal models of diabetes. However, comprehensive pharmacokinetic and pharmacodynamic studies in animal models, including detailed dosing regimens and outcome measures, have not been extensively reported in the available literature. The compound's selectivity for PTP1B over TCPTP (approximately 42-fold) is important for its in vivo efficacy and safety profile. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for JTT 551 typically involves measuring its inhibitory activity against PTP1B and TCPTP using phosphatase activity assays. The assay system includes recombinant human PTP1B or TCPTP enzyme, a suitable phosphopeptide substrate (such as p-nitrophenyl phosphate or a fluorogenic substrate like DiFMUP), and assay buffer (typically containing Tris-HCl, EDTA, and DTT at physiological pH). JTT 551 is added at varying concentrations (0.1 nM to 100 uM) and pre-incubated with the enzyme before substrate addition. The reaction is incubated at 30-37degC for 30-60 minutes, and the dephosphorylation of the substrate is monitored by measuring absorbance at 405 nm (for pNPP) or fluorescence (for DiFMUP). Ki values are calculated from dose-response curves using nonlinear regression analysis. The compound's selectivity for PTP1B over TCPTP is determined by comparing the Ki values for the two enzymes.
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| Cell Assay |
The in vitro cell-based assay for JTT 551 involves culturing relevant cell lines such as hepatocytes (HepG2), adipocytes (3T3-L1), or myocytes (C2C12) and treating them with varying concentrations of the compound to assess its effects on insulin signaling. Cells are typically seeded in multi-well plates and serum-starved before treatment. The cells are then treated with JTT 551 (0.1-100 uM) for 1-24 hours, followed by insulin stimulation. Insulin receptor phosphorylation and downstream signaling (AKT, ERK) are assessed by Western blot analysis using phospho-specific antibodies. Glucose uptake can be measured using 2-deoxyglucose uptake assays with radiolabeled or fluorescent tracers. Additionally, the compound's effects on PTP1B activity in cell lysates can be assessed using phosphatase activity assays. Cell viability is assessed using standard assays to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
In vivo animal studies for JTT 551 have been conducted to evaluate its effects on insulin sensitivity and glucose metabolism in models of type 2 diabetes mellitus. As a selective PTP1B inhibitor, JTT 551 is typically administered via oral gavage or intraperitoneal injection in rodent models of diabetes (such as db/db mice, ob/ob mice, or high-fat diet-induced obese mice). Dosing regimens typically range from 1-100 mg/kg administered daily or twice daily for 1-4 weeks. Common endpoints include fasting blood glucose levels, glucose tolerance tests, insulin tolerance tests, and HbA1c measurements. The compound's effects on body weight, food intake, and general toxicity parameters are also monitored. However, comprehensive and detailed reports of specific in vivo studies with outcome measures are limited in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of JTT 551 have been characterized to some extent. As a selective small-molecule PTP1B inhibitor, JTT 551 has a molecular weight of 605.85 g/mol and a molecular formula of C34H43N3O3S2. The compound has a purity of ≥98%. However, detailed pharmacokinetic parameters such as half-life, bioavailability, clearance, and volume of distribution have not been extensively reported in the available literature. The compound's physicochemical properties, including its lipophilicity and solubility, would influence its absorption, distribution, metabolism, and excretion profile. JTT 551 can be used in the research of type 2 diabetes mellitus, suggesting that it has suitable properties for in vivo studies.
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| Toxicity/Toxicokinetics |
JTT 551 (CAS#: 776309-04-7) is a research-grade PTP1B inhibitor with the molecular formula C34H43N3O3S2 and a molecular weight of 605.85. This compound is a selective small-molecule inhibitor of protein tyrosine phosphatase 1B (PTP1B), a key negative regulator of insulin signaling. JTT 551 exhibits Ki values of 0.22 microM for PTP1B and 9.3 microM for TCPTP (T-cell protein tyrosine phosphatase), showing approximately 42-fold selectivity for PTP1B over TCPTP. The compound can be used in the research of type 2 diabetes mellitus. By inhibiting PTP1B, JTT 551 enhances insulin receptor phosphorylation and downstream signaling, promoting glucose uptake and improving insulin sensitivity. The compound has a purity of ≥98% and is intended for research purposes only. No clinical trials or regulatory approvals have been reported.
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| References |
| Molecular Formula |
C34H43N3O3S2
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| Molecular Weight |
605.853526353836
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| Exact Mass |
605.274
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| CAS # |
776309-04-7
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| PubChem CID |
23080446
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
42
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| Complexity |
789
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(CN(CC(=O)O)CC2=NC(=CS2)C2C=CC(=CC=2)COC2C=CC(=CC=2)C(CCC)CCC)=NC=C1C(C)(C)C
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| InChi Key |
FKGBFRNVTCFMGU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C34H43N3O3S2/c1-6-8-25(9-7-2)26-14-16-28(17-15-26)40-22-24-10-12-27(13-11-24)29-23-41-32(36-29)20-37(21-33(38)39)19-31-35-18-30(42-31)34(3,4)5/h10-18,23,25H,6-9,19-22H2,1-5H3,(H,38,39)
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| Chemical Name |
2-[(5-tert-butyl-1,3-thiazol-2-yl)methyl-[[4-[4-[(4-heptan-4-ylphenoxy)methyl]phenyl]-1,3-thiazol-2-yl]methyl]amino]acetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~165.06 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6506 mL | 8.2529 mL | 16.5057 mL | |
| 5 mM | 0.3301 mL | 1.6506 mL | 3.3011 mL | |
| 10 mM | 0.1651 mL | 0.8253 mL | 1.6506 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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