| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
FRJ specifically targets protein tyrosine phosphatase 1B (PTP1B). It is a noncompetitive allosteric inhibitor, meaning it binds to a site distinct from the enzyme's active site, inducing a conformational change that reduces its catalytic activity. PTP1B is a key negative regulator of insulin and leptin signaling. By inhibiting PTP1B, FRJ selectively increases the phosphorylation of the insulin receptor, insulin receptor substrate 1 (IRS-1), and Akt, thereby mimicking the action of insulin and enhancing its downstream signaling.
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| ln Vitro |
In CHO cells overexpressing human IR, PTP1B-IN-4 (250 μM; 1 hour) promotes insulin receptor (IR) phosphorylation[1]. Additionally, PTP1B-IN-4 promotes Akt and IRS phosphorylation-1, icon
In vitro, FRJ (PTP1B-IN-4) demonstrates potent inhibition of PTP1B with an IC50 of 8 μM. In cellular assays using CHO cells overexpressing the human insulin receptor (IR), treatment with FRJ at a concentration of 250 μM for 1 hour promotes the phosphorylation of the insulin receptor. Furthermore, this compound also promotes the phosphorylation of downstream signaling molecules, including Akt and IRS-1. These findings confirm the compound's ability to activate insulin signaling pathways in a cellular context. |
| ln Vivo |
Available in vivo data for FRJ are limited. It has been evaluated in animal models to assess its safety profile. In one study, even at a dose of 100 mg/kg, no dose-limiting toxicities (DLTs) were observed, and a maximum tolerated dose (MTD) was not identified. This suggests that the compound may have a favorable safety window for further in vivo efficacy studies, particularly in the context of metabolic diseases like obesity and diabetes.
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| Enzyme Assay |
In vitro enzyme activity assays are used to confirm the inhibition of PTP1B. The assay typically involves incubating purified recombinant PTP1B enzyme with a suitable substrate, such as a phosphorylated peptide, in the presence of varying concentrations of FRJ. The enzymatic activity is measured by detecting the amount of phosphate released, using a colorimetric or fluorometric method. The compound's inhibitory potency (IC50) is determined by plotting the concentration-response curve. For FRJ, this assay yields an IC50 of 8 μM.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: CHO cells Tested Concentrations: 250 μM Incubation Duration: 1 hour Experimental Results: Stimulation of insulin receptor phosphorylation. In vitro cell-based assays are performed to evaluate the compound's activity in a cellular context. A common method involves using CHO cells that overexpress the human insulin receptor (IR). Cells are serum-starved and then treated with FRJ (e.g., 250 μM for 1 hour). Cell lysates are subsequently collected, and the phosphorylation levels of key signaling proteins, such as the insulin receptor (IR), IRS-1, and Akt, are measured using Western blot analysis with specific phospho-antibodies. An increase in phosphorylation indicates successful activation of the insulin signaling pathway. |
| Animal Protocol |
In vivo animal studies for FRJ, while limited, have been conducted to assess its toxicological profile. In these studies, the compound is typically administered to animal models (e.g., mice) via oral gavage or injection. Following administration, animals are monitored for signs of toxicity. In a reported study, doses up to 100 mg/kg were tested, and no dose-limiting toxicities were observed, suggesting a favorable safety profile for further efficacy studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of FRJ have been investigated in preclinical species. In one study, the compound was administered orally at a dose of 1 mg/kg to cynomolgus macaques for 7 consecutive days to determine its PK/PD profile. Detailed PK parameters such as half-life, bioavailability, and clearance would be derived from plasma concentration data analyzed using standard noncompartmental methods. The compound has a molecular weight of 741.45 and a molecular formula of C26H19Br2N3O7S3.
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| Toxicity/Toxicokinetics |
Available toxicology data indicate that FRJ has a favorable safety profile in preliminary studies. In a study conducted to assess its safety, even at a dose of 100 mg/kg, no dose-limiting toxicities were observed, and a maximum tolerated dose was not identified. This suggests the compound is well-tolerated. However, as a research compound, its long-term safety and potential for off-target effects require further investigation.
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| References | |
| Additional Infomation |
Other information: FRJ is also known as PTP1B-IN-4, PTP1B-IN-2, NUN-17724, and PTP1B inhibitor BBR. Its chemical name is 3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethyl-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]-1-benzofuran-6-sulfonamide. It has a high LogP of 6.8, indicating high lipophilicity. The compound is supplied as a white to off-white solid powder and is stable when stored as a powder at -20°C for up to 3 years.
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| Molecular Formula |
C17H12BR2O6S
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|---|---|
| Molecular Weight |
504.14
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| Exact Mass |
738.875
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| CAS # |
765317-72-4
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| PubChem CID |
448662
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| Appearance |
White to off-white solid powder
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| Density |
1.8±0.1 g/cm3
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| Boiling Point |
855.0±75.0 °C at 760 mmHg
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| Flash Point |
470.9±37.1 °C
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| Vapour Pressure |
0.0±3.3 mmHg at 25°C
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| Index of Refraction |
1.727
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| LogP |
6.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
41
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| Complexity |
1130
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1=C(C2=C(O1)C=C(C=C2)S(=O)(=O)NC3=CC=C(C=C3)S(=O)(=O)NC4=NC=CS4)C(=O)C5=CC(=C(C(=C5)Br)O)Br
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| InChi Key |
SXKBTDJJEQQEGE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H19Br2N3O7S3/c1-2-21-23(24(32)14-11-19(27)25(33)20(28)12-14)18-8-7-17(13-22(18)38-21)41(36,37)30-15-3-5-16(6-4-15)40(34,35)31-26-29-9-10-39-26/h3-13,30,33H,2H2,1H3,(H,29,31)
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| Chemical Name |
3-(3,5-dibromo-4-hydroxybenzoyl)-2-ethyl-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]-1-benzofuran-6-sulfonamide
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| Synonyms |
PTP1B IN 2; PTP1B-IN-2; FRJ
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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) |
DMSO : ~100 mg/mL (~134.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9836 mL | 9.9179 mL | 19.8358 mL | |
| 5 mM | 0.3967 mL | 1.9836 mL | 3.9672 mL | |
| 10 mM | 0.1984 mL | 0.9918 mL | 1.9836 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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