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| Targets |
PTP1B-IN-3 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, PTP1B-IN-3 enhances insulin signaling and promotes glucose uptake. The compound also inhibits TCPTP (T-cell protein tyrosine phosphatase) with equal potency (IC₅0 = 120 nM). Through its inhibition of these phosphatases, PTP1B-IN-3 affects multiple signaling pathways involved in metabolism, cell growth, and proliferation. Its selectivity for PTP1B and TCPTP over other phosphatases makes it a valuable tool for studying the role of these enzymes in diabetes and cancer.
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| ln Vitro |
PTP1B-IN-3 demonstrates potent in vitro inhibitory activity against PTP1B and TCPTP with IC₅0 values of 120 nM for both enzymes. This potent and selective inhibition makes it a valuable tool for studying the role of PTP1B in insulin signaling and metabolic regulation. The compound has demonstrated antidiabetic and anticancer effects in preclinical studies. By blocking the activity of PTP1B, PTP1B-IN-3 enhances insulin receptor phosphorylation and downstream signaling, promoting glucose uptake and improving insulin sensitivity. The compound's selectivity for PTP1B and TCPTP over other phosphatases has been characterized, supporting its utility as a research tool for investigating the therapeutic potential of PTP1B inhibition in metabolic disorders and cancer.
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| ln Vivo |
PTP1B-IN-3 (compound 3g) demonstrated dose-dependent reduction of glucose excursions in diet-induced obese (DIO) mice (60% inhibition at 1, 3, and 10 mg/kg, respectively). The predicted ED50 of 80% and 100%) given orally two hours prior to an oral glucose challenge is 0.8 mg/kg [1]. PTP1B-IN-3 (compound 3g; oral; 30 mg/kg for 21 days) significantly delayed the initiation of tumor formation in NDL2 Ptpn1+/+ mice (T50), extending the median number of tumor-free days from 28 days to 75 days[1]. PTP1B-IN-3 (compound 3g) demonstrated good oral bioavailability (F of 24%), slow clearance (CL of 0.71 mL/kg/min), and good elimination half-life (t1 /2, 6 hours total) in diet-induced obese (DIO) mice. In higher species, such as rats (F of 4% and squirrel monkeys (F of 2%), oral bioavailability is much lower; yet, oral dosing provides great exposure [1].
PTP1B-IN-3 has demonstrated in vivo activity as an orally active PTP1B inhibitor. The compound has shown antidiabetic and anticancer effects in preclinical studies. As an orally bioavailable compound, PTP1B-IN-3 can be administered via oral gavage in animal models, making it suitable for studying the therapeutic potential of PTP1B inhibition in metabolic disorders such as type 2 diabetes and obesity. The compound's effects on insulin sensitivity, glucose tolerance, and tumor growth have been evaluated in various animal models. However, detailed reports of specific in vivo studies, including dosing regimens, animal models, and outcome measures, are limited in the available literature. Further research is needed to fully characterize the compound's in vivo efficacy and safety profile. |
| Enzyme Assay |
The in vitro enzyme/receptor binding assay for PTP1B-IN-3 typically involves measuring its inhibitory activity against purified PTP1B and TCPTP enzymes using phosphatase activity assays. The assay system includes the recombinant 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). PTP1B-IN-3 is added at varying concentrations (typically 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. The dephosphorylation of the substrate is monitored by measuring absorbance at 405 nm (for pNPP) or fluorescence (for DiFMUP). IC₅0 values are calculated from dose-response curves using nonlinear regression analysis.
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| Cell Assay |
The in vitro cell-based assay for PTP1B-IN-3 involves culturing relevant cell lines and treating them with varying concentrations of the compound to assess its effects on insulin signaling and cell proliferation. Cells such as hepatocytes (HepG2), adipocytes (3T3-L1), or myocytes (C2C12) are typically seeded in multi-well plates and serum-starved before treatment. The cells are then treated with PTP1B-IN-3 (typically 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. For anticancer studies, cell proliferation and viability are assessed using MTT, CCK-8, or colony formation assays.
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| Animal Protocol |
In vivo animal studies for PTP1B-IN-3 have been conducted to evaluate its antidiabetic and anticancer effects. As an orally active compound, PTP1B-IN-3 is typically administered via oral gavage in rodent models of diabetes (such as db/db mice or high-fat diet-induced obese mice) or cancer xenograft models. Dosing regimens typically range from 1-100 mg/kg administered daily or twice daily for 1-4 weeks. Common endpoints in diabetic models include fasting blood glucose levels, glucose tolerance tests, insulin tolerance tests, and HbA1c measurements. In cancer models, tumor volume, tumor weight, and proliferation markers (Ki-67) are assessed. The compound's effects on body weight, food intake, and general toxicity parameters are also monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PTP1B-IN-3 have been characterized to some extent. As an orally active compound, PTP1B-IN-3 is orally bioavailable and can be administered via oral gavage in animal studies. The compound has a molecular weight of 362.06 g/mol and a molecular formula of C12H₇BrF2NO3P. Its chemical structure includes a difluoromethylphosphonate group, which is a common pharmacophore for PTP1B inhibitors. The compound has a predicted LogP value and other physicochemical properties consistent with oral bioavailability. However, detailed pharmacokinetic parameters such as half-life, Cmax, AUC, and bioavailability have not been extensively reported in the available literature. The compound is intended for research purposes only and is not approved for clinical use.
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| Toxicity/Toxicokinetics |
PTP1B-IN-3 (CAS#: 809272-64-8) is a research-grade PTP1B inhibitor with the molecular formula C12H₇BrF2NO3P and a molecular weight of 362.06. This compound exhibits potent and selective inhibition of protein tyrosine phosphatase 1B (PTP1B) and TCPTP with IC₅0 values of 120 nM for both enzymes. PTP1B-IN-3 is orally active and has demonstrated antidiabetic and anticancer effects in preclinical studies. By blocking the activity of PTP1B, the compound enhances insulin signaling and promotes glucose uptake. It is used in research focused on the inhibition of PTP1B and its therapeutic potential in metabolic disorders and cancer. The compound is intended for research purposes only. No clinical trials or regulatory approvals have been reported for PTP1B-IN-3.
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| References |
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| Additional Infomation |
[(3-bromo-7-cyano-2-naphthyl)-difluoromethyl]phosphonic acid is a member of the naphthalene family of compounds.
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| Molecular Formula |
C12H7BRF2NO3P
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| Molecular Weight |
362.063450098038
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| Exact Mass |
360.931
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| CAS # |
809272-64-8
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| Related CAS # |
PTP1B-IN-3 diammonium;2702673-78-5
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| PubChem CID |
24857885
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| Appearance |
White to off-white solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
475
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC2=CC(=C(C=C2C=C1C#N)C(F)(F)P(=O)(O)O)Br
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| InChi Key |
BWJOQFMMTKEZGA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H7BrF2NO3P/c13-11-5-8-2-1-7(6-16)3-9(8)4-10(11)12(14,15)20(17,18)19/h1-5H,(H2,17,18,19)
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| Chemical Name |
[(3-bromo-7-cyanonaphthalen-2-yl)-difluoromethyl]phosphonic 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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.7620 mL | 13.8099 mL | 27.6197 mL | |
| 5 mM | 0.5524 mL | 2.7620 mL | 5.5239 mL | |
| 10 mM | 0.2762 mL | 1.3810 mL | 2.7620 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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