| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
IC50: 120 nM (PTP1B), 120 nM (TCPTP)[2]
PTP1B (IC50 = 120 nM) and TCPTP (IC50 = 120 nM). PTP1B-IN-3 diammonium is a potent and orally active PTP1B inhibitor that also inhibits TCPTP with equal potency. It is a specific inhibitor with anti-diabetic and anti-cancer effects. |
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| ln Vitro |
PTP1B-IN-3 diammonium inhibits PTP1B and TCPTP with IC50 values of 120 nM for both phosphatases. By blocking PTP1B, a negative regulator of insulin signaling, it enhances insulin receptor phosphorylation and downstream AKT activation. This leads to improved insulin sensitivity and glucose uptake in vitro. The dual inhibition of TCPTP may contribute to its anti-cancer effects.
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| ln Vivo |
When administered orally two hours prior to an oral glucose challenge, PTP1B-IN-3 (compounds 3g) in diet-induced obese (DIO) mice shows dose-dependent suppression (60%, 80%, and 100% inhibition at 1, 3 and 10 mg/kg, respectively) of glucose excursion with an estimated ED50 of 0.8 mg/kg[1]. PTP1B-IN-3 (compounds 3g; oral; 30 mg/kg for 21 days) greatly delays the initiation of tumor formation in NDL2 Ptpn1+/+ mice, prolonging the median tumor free days (T50) from 28 days to 75 days in NDL2 Ptpn1 transgenic mice[1]. PTP1B-IN-3 (compounds 3g) shows good oral bioavailability (F of 24%), slow clearance (CL of 0.71 mL/kg/min), and good elimination half-life (t1/2 of 6 h) in diet-induced obese (DIO) mice. Higher species such as rats (F of 4%) and squirrel monkeys (F of 2%) have significantly reduced oral bioavailability; yet, oral dosage results in excellent exposures[1].
In vivo, PTP1B-IN-3 diammonium is orally active and enhances insulin sensitivity in animal models of type 2 diabetes and obesity. By inhibiting PTP1B, it improves glucose tolerance and reduces blood glucose levels. It also exhibits anti-cancer effects in tumor models by modulating growth factor signaling. These properties make it a promising candidate for metabolic and cancer research. |
| Enzyme Assay |
For non-cellular assays, recombinant human PTP1B or TCPTP is incubated with a fluorogenic substrate such as DiFMUP (6,8-difluoro-4-methylumbelliferyl phosphate) in assay buffer. PTP1B-IN-3 diammonium is added at varying concentrations (1-1000 nM). Fluorescence is measured (excitation 360 nm, emission 460 nm), and IC50 values are calculated from dose-response curves. Selectivity is assessed against other phosphatases.
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| Cell Assay |
For cell-based assays, hepatocytes (e.g., HepG2) or myotubes are treated with PTP1B-IN-3 diammonium (50-500 nM) for 2-24 hours, then stimulated with insulin. Insulin receptor (IR) and AKT phosphorylation are measured by Western blot using phospho-specific antibodies. Glucose uptake is assessed using 2-deoxyglucose assays. Cellular PTP1B activity in lysates is measured using fluorogenic substrates. Cancer cell proliferation is assessed by MTT assays.
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| Animal Protocol |
For animal studies, PTP1B-IN-3 diammonium is administered orally to mouse models of type 2 diabetes (e.g., db/db mice or diet-induced obesity models). Doses typically range from 10-50 mg/kg once daily. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) are performed. Blood glucose and insulin levels are measured. In tumor models, tumor volume is monitored. Liver and muscle tissues are collected for analysis of insulin signaling markers.
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| ADME/Pharmacokinetics |
PTP1B-IN-3 diammonium is orally bioavailable with favorable pharmacokinetic properties. It is typically formulated in 0.5% methylcellulose or other oral vehicles for in vivo administration. The compound has a molecular weight of 396.12. Detailed PK parameters (half-life, Cmax, AUC) are available in the literature from preclinical studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have shown PTP1B-IN-3 diammonium to be well tolerated at therapeutic doses (10-50 mg/kg). No significant off-target toxicity or organ damage has been reported in animal studies. As an investigational research compound, it should be handled following standard safety protocols. It is not intended for human use.
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| References |
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| Additional Infomation |
PTP1B-IN-3 diammonium (CAS: 2702673-78-5) has a molecular formula of C12H13BrF2N3O3P·2NH3 and a molecular weight of 396.12. It is a potent and orally active PTP1B inhibitor with equal activity against TCPTP. It is a valuable tool for studying insulin resistance, type 2 diabetes, obesity, and cancer. It is not approved for clinical use.
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| Exact Mass |
394.985
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|---|---|
| CAS # |
2702673-78-5
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| Related CAS # |
PTP1B-IN-3;809272-64-8
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| PubChem CID |
162641761
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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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.N.N
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| InChi Key |
DKKOXAMRGUYZIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H7BrF2NO3P.2H3N/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);2*1H3
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| Chemical Name |
azane;[(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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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.) |
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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