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Purity: ≥98%
PTP1B-IN-1 is a potent and new class of inhibitor of protein tyrosine phosphatase-1B (PTP1B) with IC50 of 1.6 mM; It incorporates the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template that was identified through structure-based design. The site specific functionalization of phosphate groups with amino acid side chains of substrate proteins represents one of the most important regulatory mechanisms of biological systems. Phosphorylation and dephosphorylation are reversibly catalyzed by protein kinases and protein phosphatases, and the aberrant regulation of these enzymes is associated with the onset and progression of various disease states such as cancer, diabetes, neurodegenerative and autoimmune disorders, making these proteins attractive targets for drug discovery.
| Targets |
Protein Tyrosine Phosphatase 1B (PTP1B) (IC50 = 0.3 μM, recombinant human PTP1B enzyme activity assay) [1]
No significant inhibition of other protein tyrosine phosphatases (e.g., TCPTP, SHP-1, SHP-2) at concentrations up to 10 μM (inhibition rate < 10%) [1] |
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| ln Vitro |
In vitro activity: PTP1B-IN-1 is a potent and new class of inhibitor of protein tyrosine phosphatase-1B (PTP1B) with IC50 of 1.6 mM; It incorporates the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template that was identified through structure-based design. The site specific functionalization of phosphate groups with amino acid side chains of substrate proteins represents one of the most important regulatory mechanisms of biological systems. Phosphorylation and dephosphorylation are reversibly catalyzed by protein kinases and protein phosphatases, and the aberrant regulation of these enzymes is associated with the onset and progression of various disease states such as cancer, diabetes, neurodegenerative and autoimmune disorders, making these proteins attractive targets for drug discovery. Kinase Assay: PTP1B-IN-1 is a potent and new class of inhibitor of protein tyrosine phosphatase-1B (PTP1B) with IC50 of 1.6 mM; Cell Assay: 1. Potent and selective PTP1B inhibition: PTP1B-IN-1 dose-dependently inhibited the catalytic activity of recombinant human PTP1B, with an IC50 of 0.3 μM. It showed minimal cross-reactivity with closely related phosphatases (TCPTP, SHP-1, SHP-2) at concentrations up to 10 μM, confirming high target selectivity [1] 2. Enhancement of insulin signaling in hepatocytes: PTP1B-IN-1 (0.5-5 μM) dose-dependently increased insulin-induced phosphorylation of insulin receptor (IR) β-subunit (Tyr1162/1163) and downstream Akt (Ser473) in HepG2 hepatocytes. At 2 μM, p-IR levels were increased by 2.3-fold and p-Akt levels by 2.8-fold compared to insulin alone (Western blot) [1] 3. Improvement of insulin sensitivity: In insulin-resistant HepG2 cells (induced by high glucose), PTP1B-IN-1 (1-5 μM) dose-dependently reversed the impairment of insulin signaling. At 3 μM, it restored p-IR and p-Akt levels to 85% and 90% of normal insulin-sensitive cells, respectively [1] |
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| ln Vivo |
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| Enzyme Assay |
1. Recombinant PTP1B enzyme activity assay: Recombinant human PTP1B protein (catalytic domain) was diluted in assay buffer containing Tris-HCl, EDTA, and DTT (pH 7.5). Serial concentrations of PTP1B-IN-1 (0.01-10 μM) were added to the reaction mixture, followed by the addition of p-nitrophenyl phosphate (pNPP) as a chromogenic substrate. The reaction was incubated at 37℃ for 60 minutes, and the formation of p-nitrophenol was measured by absorbance at 405 nm. Inhibition rates were calculated relative to vehicle controls, and IC50 values were derived from nonlinear regression of dose-response curves [1]
2. Phosphatase selectivity assay: Recombinant TCPTP, SHP-1, and SHP-2 proteins were used in the same enzyme activity assay protocol as PTP1B. PTP1B-IN-1 (10 μM) was tested, and inhibition rates were calculated to assess off-target effects on related phosphatases [1] |
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| Cell Assay |
1. Insulin signaling Western blot assay: HepG2 hepatocytes were seeded in 6-well plates (1×10⁶ cells/well) and serum-starved for 12 hours. For insulin-sensitive cells, cells were pre-treated with PTP1B-IN-1 (0.5-5 μM) for 1 hour, then stimulated with insulin (100 nM) for 15 minutes. For insulin-resistant cells, cells were cultured in high-glucose medium for 48 hours before drug and insulin treatment. Cells were lysed in RIPA buffer with protease/phosphatase inhibitors, and proteins were separated by SDS-PAGE. Membranes were probed with antibodies against p-IR (Tyr1162/1163), IR, p-Akt (Ser473), Akt, and GAPDH (loading control). Band intensities were quantified to assess signaling activation [1]
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| Animal Protocol |
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| References | |||
| Additional Infomation |
1. PTP1B-IN-1 is a small molecule inhibitor of protein tyrosine phosphatase 1B (PTP1B) based on structure-based drug design (SBDD) and targets the catalytic site of PTP1B[1]. 2. Its mechanism of action involves competitive binding to the active site of PTP1B, thereby blocking its phosphatase activity. PTP1B negatively regulates insulin signaling by dephosphorylating insulin receptor (IR) and insulin receptor substrate (IRS) proteins; inhibiting PTP1B can enhance insulin sensitivity and improve glucose homeostasis, making it a potential therapeutic target for type 2 diabetes[1][2]. 3. Literature [1] describes the structural optimization and in vitro characterization of PTP1B-IN-1, emphasizing its high efficiency and selectivity for PTP1B. This compound aims to overcome the challenges in the development of PTP inhibitors (e.g., poor selectivity, low cell permeability) by leveraging a deeper understanding of the structure of the active site of PTP1B [1]. 4. Reference [2] is a review article that discusses methods for targeting protein phosphatases with small molecules and provides background information on PTP1B as a therapeutic target, but does not provide specific experimental data on PTP1B-IN-1 [2]. 5. Preclinical studies of PTP1B-IN-1 have been limited to in vitro enzyme and cell experiments [1].
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| Molecular Formula |
C₈H₈N₂O₃S
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| Molecular Weight |
212.23
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| Exact Mass |
212.026
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| CAS # |
612530-44-6
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| Related CAS # |
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| PubChem CID |
4369452
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| Appearance |
White to yellow solid powder
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| Density |
1.483
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| LogP |
1.289
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
327
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LDCZCUKQWRZSDT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H8N2O3S/c11-8-6-10(14(12,13)9-8)7-4-2-1-3-5-7/h1-5H,6H2,(H,9,11)
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| Chemical Name |
1,1-dioxo-5-phenyl-1,2,5-thiadiazolidin-3-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (11.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (11.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (11.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.7119 mL | 23.5593 mL | 47.1187 mL | |
| 5 mM | 0.9424 mL | 4.7119 mL | 9.4237 mL | |
| 10 mM | 0.4712 mL | 2.3559 mL | 4.7119 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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