| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Ki: 20 nM (IRAP)[1]
HFI-437 targets insulin-regulated aminopeptidase (IRAP), also known as oxytocinase or cystinyl aminopeptidase. IRAP is a zinc-dependent metallopeptidase that belongs to the M1 family of aminopeptidases. It is a type II integral membrane protein that is primarily localized to intracellular vesicles, including GLUT4-containing vesicles in adipocytes and muscle cells. IRAP plays a role in the regulation of glucose uptake by mediating the trafficking of GLUT4 transporters to the plasma membrane in response to insulin. Additionally, IRAP has been implicated in the degradation of neuropeptides such as vasopressin and oxytocin, and its inhibition has been shown to enhance cognitive function in animal models. HFI-437 exhibits a Ki of 20 nM for IRAP, indicating high-affinity binding. The compound is non-peptidic, which offers advantages over peptide-based inhibitors in terms of stability and oral bioavailability. |
|---|---|
| ln Vitro |
In vitro, HFI-437 demonstrates potent inhibition of insulin-regulated aminopeptidase (IRAP) with a Ki of 20 nM. The compound's inhibitory activity has been characterized in enzyme assays using recombinant IRAP or IRAP-containing membrane preparations. As a non-peptidic inhibitor, HFI-437 offers advantages over peptide-based inhibitors, including improved stability and potentially better cell permeability. The compound's potent inhibition of IRAP suggests that it effectively blocks the enzyme's catalytic activity, preventing the cleavage of its peptide substrates. This inhibition is expected to modulate the physiological functions of IRAP, including its role in glucose uptake regulation and neuropeptide metabolism. However, specific quantitative data beyond the Ki value and detailed structure-activity relationship studies have not been extensively reported in the available literature.
|
| ln Vivo |
In vivo activity of HFI-437 has been demonstrated in the context of cognitive enhancement. As a cognitive enhancer, the compound has been shown to improve cognitive function in animal models. However, specific details regarding the animal models used, dosing regimens, and quantitative outcomes are not extensively reported in the available literature. Based on its mechanism as an IRAP inhibitor, HFI-437 would be expected to enhance cognitive performance by modulating the levels of neuropeptides such as vasopressin and oxytocin, which are involved in learning and memory processes. The compound's non-peptidic nature suggests that it may have favorable pharmacokinetic properties compared to peptide-based IRAP inhibitors, potentially allowing for oral administration. Further in vivo studies would be required to fully characterize its efficacy, dose-response relationship, and duration of action.
|
| Enzyme Assay |
In vitro enzyme assay protocols for HFI-437 typically involve measuring the inhibition of IRAP enzymatic activity using fluorogenic or chromogenic peptide substrates. A standard protocol would involve incubating recombinant human IRAP or IRAP-containing membrane preparations with varying concentrations of HFI-437 (typically 0.1 nM to 10 μM) and a fluorogenic substrate such as Leu-AMC (leucine-7-amido-4-methylcoumarin) or a related aminopeptidase substrate in assay buffer (e.g., Tris-HCl, pH 7.4, with appropriate salts) at 37°C for a defined period (e.g., 30-60 minutes). The reaction is terminated by the addition of a stopping solution (e.g., acetic acid or sodium acetate buffer), and fluorescence is measured using a fluorescence plate reader with excitation at ~380 nm and emission at ~460 nm. The rate of substrate cleavage is calculated, and IC50 values are determined from concentration-response curves. Ki values are derived using appropriate kinetic models.
|
| Cell Assay |
In vitro cell-based assay protocols for HFI-437 would typically involve assessing its effects on IRAP activity in cultured cells expressing the enzyme. A standard protocol could use HEK293 or other cell lines transfected with human IRAP. Cells are seeded in multi-well plates and treated with varying concentrations of HFI-437 (typically 0.1 nM to 10 μM) for a defined period (e.g., 1-24 hours). Following treatment, cells are lysed, and IRAP activity is measured in cell lysates using fluorogenic substrates as described for enzyme assays. Alternatively, the effects of HFI-437 on cellular functions mediated by IRAP, such as glucose uptake, could be assessed. For glucose uptake assays, cells are treated with HFI-437 in the presence or absence of insulin, and glucose uptake is measured using radiolabeled 2-deoxyglucose or fluorescent glucose analogs. Cell viability should be assessed using MTT or similar assays to ensure that observed effects are not due to cytotoxicity. Appropriate controls include vehicle-treated cells and cells treated with a known IRAP inhibitor.
|
| Animal Protocol |
In vivo animal experimental protocols for HFI-437 would typically involve administering the compound to rodents and assessing its effects on cognitive function. A standard protocol might involve oral gavage or intraperitoneal injection of HFI-437 at doses ranging from 1 to 30 mg/kg, based on preliminary dose-finding studies. The compound can be formulated using standard vehicles such as 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline. Cognitive function is assessed using behavioral tests such as the Morris water maze (spatial learning and memory), novel object recognition (recognition memory), or passive avoidance (fear conditioning memory). Treatment is typically administered prior to training and testing sessions, and performance is compared to vehicle-treated control groups. Additional endpoints may include assessment of IRAP activity in brain tissue, measurement of neuropeptide levels, and evaluation of potential side effects. Pharmacodynamic studies may involve measuring drug concentrations in plasma and brain tissue to establish exposure-response relationships.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of HFI-437 have not been extensively characterized in published studies. The compound has a molecular weight of 404.42, which is within the range favorable for oral bioavailability. Its non-peptidic nature suggests that it may have improved stability and permeability compared to peptide-based inhibitors. The compound is supplied as a powder and should be stored at -20°C for up to 3 years or in solvent at -80°C for up to 1 year. For in vivo studies, the compound can be formulated using vehicles such as 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline. However, specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The compound's protein binding, metabolism, and routes of elimination remain uncharacterized. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile.
|
| Toxicity/Toxicokinetics |
Toxicological data for HFI-437 are limited, as the compound is intended for research use only and has not undergone systematic toxicity testing. No acute toxicity (LD50), subchronic toxicity, genotoxicity, or reproductive toxicity studies have been reported specifically for this compound. As with all research chemicals, appropriate safety precautions should be taken when handling the compound, including working in a fume hood, wearing appropriate personal protective equipment, and avoiding inhalation, ingestion, or skin contact. The compound is not intended for human use. Researchers should consult the material safety data sheet (MSDS) for specific safety information and handling recommendations. The compound should be stored under recommended conditions to maintain stability.
|
| References | |
| Additional Infomation |
HFI-437 is a research-grade compound that functions as a potent, non-peptidic inhibitor of insulin-regulated aminopeptidase (IRAP) with a Ki of 20 nM. It also acts as a cognitive enhancer, making it a valuable tool for studying the role of IRAP in cognitive function and for exploring the potential of IRAP inhibitors as therapeutics for cognitive disorders. The compound has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves high-affinity inhibition of IRAP, which modulates the levels of neuropeptides involved in learning and memory and potentially enhances cognitive performance. The compound is non-peptidic, offering advantages in terms of stability and potential oral bioavailability compared to peptide-based inhibitors. HFI-437 is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
|
| CAS # |
1110650-74-2
|
|---|---|
| Appearance |
Off-white to light yellow solid powder
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO :~100 mg/mL (~247.27 mM; with sonication)
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
