| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
IC50: 0.43 μM (human FATP1)[1]. IC50: 0.39 μM (mouse FATP1)[1]
FATP1-IN-2 specifically targets fatty acid transport protein 1 (FATP1). FATP1 is a transmembrane protein that facilitates the cellular uptake of long-chain fatty acids and is highly expressed in adipose tissue, skeletal muscle, and heart. FATP1-IN-2 acts as a potent and orally active inhibitor. The compound demonstrates IC50 values of 0.43 microM for the human FATP1 protein and 0.39 microM for the mouse FATP1 protein.. |
|---|---|
| ln Vitro |
In vitro, FATP1-IN-2 is a potent FATP1 inhibitor. It shows high inhibitory activity against the human FATP1 protein with an IC50 of 0.43 uM and against the mouse FATP1 protein with an IC50 of 0.39 uM.. This data indicates that it is a similarly potent inhibitor across species and operates at sub-micromolar concentrations. By blocking FATP1-mediated fatty acid uptake, it reduces the accumulation of lipids within cells.
|
| ln Vivo |
The mouse IC50 value is less than the Cmax values of FATP1-IN-2 (10 mg/kg; oral)[1]. For four weeks, FATP1-IN-2 (3, 10, and 30 mg/kg; orally delivered) did not alter the amount of TG present in any tissue, regardless of dose[1].
Specific in vivo activity data for FATP1-IN-2 has not been detailed in the provided search results. However, as an orally active FATP1 inhibitor, it is hypothesized to improve insulin sensitivity and reduce body weight in animal models of obesity and type 2 diabetes (e.g., high-fat diet-fed mice). By blocking lipid uptake into adipose tissue and muscle, FATP1-IN-2 may prevent lipid-induced insulin resistance. The compound is used in research on obesity, insulin resistance, type 2 diabetes, and cardiovascular diseases linked to dysregulated lipid uptake.. |
| Enzyme Assay |
The specific in vitro protocol for assessing FATP1 inhibition is a [14C]-labeled fatty acid uptake assay using cells overexpressing FATP1. HEK-293 cells or CHO cells stably transfected with human FATP1 are seeded in 24-well plates. After reaching confluency, the cells are washed and pre-incubated with varying concentrations of FATP1-IN-2 (0.001-1000 uM) in serum-free medium for 15 minutes. Then, [14C]-oleic acid (a long-chain fatty acid, 10 uM, 0.5 uCi) is added to the cells, typically complexed with bovine serum albumin (BSA) to mimic physiological conditions. After a 5-10 minute incubation at 37degC, the uptake reaction is terminated by washing the cells three times with ice-cold PBS containing 0.1% BSA to remove surface-bound fatty acids. The cells are lysed with 0.2 N NaOH, and the radioactivity is measured by liquid scintillation counting. The IC50 is calculated from the inhibition curve.
|
| Cell Assay |
The in vitro cellular assay for FATP1-IN-2 involves the use of primary human adipocytes or murine 3T3-L1 differentiated adipocytes. The adipocytes are seeded in 96-well black-walled plates and differentiated into mature fat cells over 7-14 days. The cells are then serum-starved for 3-4 hours. A fluorescently labeled long-chain fatty acid (e.g., BODIPY-FL C16 or C12) is used as the substrate. Varying concentrations of FATP1-IN-2 (0.01-100 uM) are added to the cells and incubated for 15-30 minutes. The fluorescent fatty acid analog is then added to the wells, and the cells are incubated for an additional 10-30 minutes. The cells are washed three times with PBS containing 0.1% BSA to remove extracellular fluorescence. Intracellular fluorescence (indicating fatty acid uptake) is measured using a fluorescence plate reader (Ex/Em = 485/520 nm). The IC50 is calculated from the dose-response curve. Cell viability is assessed using the MTT assay to ensure that the inhibition is not due to toxicity.
|
| Animal Protocol |
Animal/Disease Models: Mice[1]
Doses: 10 mg/kg Route of Administration: Po Experimental Results: demonstrated a Cmax value above the mouse IC50 value. An in vivo protocol for FATP1-IN-2 would involve a high-fat diet (HFD)-induced obesity mouse model. Male C57BL/6J mice are placed on a 60% high-fat diet for 12 weeks to induce obesity, insulin resistance, and fatty liver. Mice are then randomized into treatment groups. FATP1-IN-2 is formulated in a suitable vehicle (e.g., 10% DMSO/40% PEG300/5% Tween-80/45% saline) and administered orally by gavage at doses of 10, 30, and 60 mg/kg once daily for 4 weeks. Body weight and food intake are measured weekly. An oral glucose tolerance test (OGTT) is performed at week 4. At the end of the study, blood is collected for serum insulin, glucose, and lipid profile analysis. Adipose tissue, skeletal muscle, and liver are harvested for histological analysis (e.g., H&E staining to measure adipocyte size) and to measure tissue triglyceride content. Insulin signaling in these tissues is assessed by Western blotting for phosphorylated AKT (p-AKT). |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for FATP1-IN-2 is not publicly available. However, it is classified as an orally active compound, indicating that it has sufficient oral bioavailability to be effective. A standard PK study would involve oral (PO) administration (10 mg/kg) and intravenous (IV) administration (1 mg/kg) in mice. Blood samples are collected at multiple time points (0-24 h), and plasma concentrations of FATP1-IN-2 are quantified by LC-MS/MS. Key PK parameters, including terminal half-life (T1/2), maximum plasma concentration (Cmax), area under the curve (AUC), and oral bioavailability (F%), would be calculated using non-compartmental analysis.
|
| Toxicity/Toxicokinetics |
Specific toxicological data for FATP1-IN-2 is not available. As an inhibitor of fatty acid uptake, the primary safety concern is the potential for off-target effects on other fatty acid transporters (e.g., FATP2, FATP4) or on essential metabolic pathways in the liver and heart. Standard safety screening would include a broad panel of target selectivity assays (e.g., Eurofins CEREP) to assess binding to other transporters and receptors. An in vitro hERG (human Ether-à-go-go-Related Gene) channel assay would be performed to assess the risk of QT prolongation. A 14-day repeat-dose oral toxicity study in rats would be conducted to determine the maximum tolerated dose (MTD) and to identify any target organ toxicity, particularly in the liver and kidneys.
|
| References | |
| Additional Infomation |
FATP1-IN-2 is a research-grade chemical and is not approved for clinical use. It is a potent and orally active inhibitor of fatty acid transport protein 1 (FATP1), with IC50 values of 0.43 microM (human) and 0.39 microM (mouse).. This compound is a valuable tool for studying the role of FATP1 in metabolic diseases, including obesity, type 2 diabetes, and insulin resistance. It is for research use only and is typically stored at -20degC for long-term stability.
|
| Molecular Formula |
C19H20FN5O
|
|---|---|
| Molecular Weight |
353.39
|
| Exact Mass |
353.165
|
| CAS # |
2650944-83-3
|
| PubChem CID |
71601851
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
3.2
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
498
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(=O)(C1N2C(=NC=1C)C=CC=C2)CN1CCN(C2=NC=C(F)C=C2)CC1
|
| InChi Key |
ZGLMIQGBDRQCKA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H20FN5O/c1-14-19(25-7-3-2-4-18(25)22-14)16(26)13-23-8-10-24(11-9-23)17-6-5-15(20)12-21-17/h2-7,12H,8-11,13H2,1H3
|
| Chemical Name |
2-[4-(5-fluoropyridin-2-yl)piperazin-1-yl]-1-(2-methylimidazo[1,2-a]pyridin-3-yl)ethanone
|
| 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 (282.97 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (14.15 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 50.0 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: ≥ 5 mg/mL (14.15 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 50.0 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: ≥ 5 mg/mL (14.15 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 | 2.8297 mL | 14.1487 mL | 28.2973 mL | |
| 5 mM | 0.5659 mL | 2.8297 mL | 5.6595 mL | |
| 10 mM | 0.2830 mL | 1.4149 mL | 2.8297 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
