| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
ABT-046 targets DGAT-1 (diacylglycerol acyltransferase 1), an enzyme that catalyzes the final and committed step in triglyceride synthesis. DGAT-1 transfers an acyl group from acyl-CoA to diacylglycerol to form triglycerides. DGAT-1 is predominantly expressed in the intestine and adipose tissue and plays a critical role in dietary fat absorption and storage. By inhibiting DGAT-1, ABT-046 reduces triglyceride synthesis and absorption, making it a potential therapeutic target for obesity and metabolic disorders. ABT-046 is a potent and selective DGAT-1 inhibitor with IC50 values of 8 nM against both human and mouse DGAT-1. The compound shows no inhibition against human DGAT-2.
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| ln Vitro |
ABT-046 can prevent the synthesis of triglycerides in HeLa cells that express human DGAT-1 with an IC50 of 78 nM, however it has no inhibitory impact on human DGAT-2[1]. When tested in Caco-2 cells, ABT-046 had high in vitro permeability values but no sign of active efflux (efflux ratios of 1.4 and 1.1 at 0.5 and 5 μM, respectively) [1]. In microsomal preparations from mouse and human livers, ABT-046 has very little turnover [1].
ABT-046 demonstrates potent in vitro activity as a DGAT-1 inhibitor. The compound inhibits human and mouse DGAT-1 with IC50 values of 8 nM. ABT-046 shows no inhibition against human DGAT-2. In HeLa cells expressing human DGAT-1, ABT-046 inhibits triglyceride formation with an IC50 of 78 nM. In Caco-2 cells, ABT-046 exhibits high permeability and no active efflux (efflux ratios of 1.4 and 1.1 at 0.5 and 5 μM, respectively). The compound's potent and selective DGAT-1 inhibition makes it a valuable tool for studying the role of DGAT-1 in lipid metabolism and metabolic diseases. |
| ln Vivo |
In CD-1 mice, ABT-046 (0.03-3 mg/kg; ig; once) dramatically lowers postprandial triglycerides [1]. In diet-induced obese mice, ABT-046 (0.3 mg/kg; ir; once) eliminates postprandial triglyceride fluctuations [1].
ABT-046 has been evaluated in vivo for its effects on lipid metabolism. Oral administration of ABT-046 at doses ≥0.03 mg/kg significantly reduced postprandial triglycerides in mice following an oral lipid challenge. The compound's oral activity and efficacy in reducing postprandial triglycerides support its utility for studying DGAT-1 inhibition as a therapeutic strategy for metabolic diseases such as obesity, dyslipidemia, and non-alcoholic fatty liver disease. ABT-046's selectivity for DGAT-1 over DGAT-2 may offer advantages in terms of reduced side effects. Detailed in vivo efficacy data, including dose-response relationships, are available in the primary literature. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for ABT-046 measures the inhibition of DGAT-1 enzymatic activity. Recombinant human or mouse DGAT-1 enzyme is incubated with varying concentrations of ABT-046 (typically ranging from picomolar to micromolar) in the presence of diacylglycerol substrate and acyl-CoA donor (e.g., oleoyl-CoA or palmitoyl-CoA). The enzymatic reaction is monitored by measuring the production of triglycerides using chromatographic (LC-MS), radiometric, or fluorescence-based methods. IC50 values are determined by fitting dose-response curves to the inhibition data (8 nM for human and mouse DGAT-1). The compound is dissolved in DMSO and diluted in assay buffer. Selectivity is assessed by testing the compound against DGAT-2 and other related enzymes. Appropriate positive controls and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for ABT-046 is performed using HeLa cells expressing human DGAT-1 or Caco-2 intestinal epithelial cells. Cells are cultured in appropriate medium and treated with varying concentrations of ABT-046 or vehicle control (DMSO). Triglyceride synthesis is measured by incubating cells with radiolabeled fatty acids or glycerol and quantifying the incorporation of label into triglycerides. The inhibition of triglyceride formation is quantified, and IC50 values are determined (78 nM in HeLa cells expressing human DGAT-1). Permeability and efflux ratios are assessed in Caco-2 cells to evaluate intestinal absorption and potential efflux mechanisms. The compound's effects on cellular lipid metabolism can also be assessed by measuring lipid accumulation.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6J diet-induced obesity (DIO) mice [1]
Doses: 0.3 mg/kg Route of Administration: po (oral gavage), single dose Experimental Results: Serum triglyceride concentration continued to decrease throughout the experiment. Animal/Disease Models: CD-1 mice and SD (SD (Sprague-Dawley)) rats [1] Doses: 10 mg/kg or 5 mg/kg Route of Administration: intravenous (iv) (iv)injection or po (oral gavage) (pharmacokinetic/PK/PK analysis) Experimental Results: ABT-046a [1] Selected pharmacokinetic/PK/PK properties in mouse (10 mg/kg) Rat (5 mg/kg) ivb T1/2 (h) 4.6 3.8 Vss (L/kg) 0.3 0.3 Clp (L/h/ kg) 0.1 0.05 pob T1/2 (h) 5.1 5.6 Cmax (μg/mL) 17.4 9.3 AUC (μg·h/mL) 151 130 F (%) 78 91 a All values are mean ± SEM (unless otherwise Note, n = 3). b 1% Tween-80 aqueous solution. In vivo animal experiments with ABT-046 are conducted using rodent models to assess the compound's effects on postprandial triglyceride metabolism. ABT-046 is administered orally at various doses (≥0.03 mg/kg). Following an oral lipid challenge, blood samples are collected at various time points, and plasma triglyceride levels are measured. The reduction in postprandial triglycerides is quantified and compared to vehicle-treated controls. The compound's effects on body weight, food intake, and other metabolic parameters can also be assessed in longer-term studies. Detailed experimental protocols, including dosing regimens and endpoints, are described in the primary literature. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for ABT-046 are partially documented. The compound is orally active and shows high permeability in Caco-2 cells with no active efflux (efflux ratios of 1.4 and 1.1 at 0.5 and 5 μM). ABT-046 has a molecular weight of 350.41 and a chemical formula of C20H22N4O2. The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, ABT-046 is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for ABT-046 are not extensively documented in publicly available sources. As a research-grade compound, ABT-046 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References | |
| Additional Infomation |
ABT-046 is a research compound developed for studying the role of DGAT-1 in lipid metabolism and metabolic diseases. The compound is a potent, selective, and orally active DGAT-1 inhibitor with IC50 values of 8 nM against human and mouse DGAT-1 and no inhibition of DGAT-2. ABT-046 significantly reduces postprandial triglycerides in mice following oral administration at doses ≥0.03 mg/kg. The compound's selectivity for DGAT-1 over DGAT-2 makes it a valuable tool for dissecting the specific functions of DGAT-1 in triglyceride synthesis and metabolism. ABT-046 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical metabolic research. ABT-046 is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C20H22N4O2
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| Molecular Weight |
350.41428
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| Exact Mass |
350.174
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| CAS # |
1031336-60-3
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| PubChem CID |
56933229
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| Appearance |
White to off-white solid powder
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| LogP |
4.308
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
486
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BWUXSHHOKODNAK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N4O2/c21-20-17(12-22-18-9-10-23-24(18)20)16-7-5-15(6-8-16)14-3-1-13(2-4-14)11-19(25)26/h5-10,12-14H,1-4,11,21H2,(H,25,26)
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| Chemical Name |
2-[4-[4-(7-aminopyrazolo[1,5-a]pyrimidin-6-yl)phenyl]cyclohexyl]acetic acid
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| Synonyms |
ABT-046; ABT 046; ABT046.
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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 : ~66.67 mg/mL (~190.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.77 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 16.7 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. Solubility in Formulation 2: ≥ 1.67 mg/mL (4.77 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 16.7 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 | 2.8538 mL | 14.2690 mL | 28.5380 mL | |
| 5 mM | 0.5708 mL | 2.8538 mL | 5.7076 mL | |
| 10 mM | 0.2854 mL | 1.4269 mL | 2.8538 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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