| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Peroxisome proliferator-activated receptor-alpha (PPAR-α). KDS-5104 (AM-3102) is a hydrolysis-resistant analog of oleoylethanolamide (OEA) that acts as a potent PPAR-α agonist. In a cell-based transactivation assay using HeLa cells expressing the PPAR-α ligand-binding domain, KDS-5104 stimulated transcriptional activity with an EC₅₀ of 100 ± 21 nM (n=11). It did not activate PPAR-γ at concentrations up to 10 μM. [1]
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|---|---|
| ln Vitro |
KDS-5104 was highly resistant to enzymatic hydrolysis by mouse liver homogenates, which contain the OEA-hydrolyzing enzymes FAAH and NAAA. After 60 minutes of incubation, KDS-5104 showed minimal degradation, whereas OEA was rapidly hydrolyzed with a half-life (t₁/₂) of 14 ± 3 minutes. The hydrolysis-resistant property was attributed to increased steric bulk around the amide bond. [1]
In a PPAR-α transactivation assay using HeLa cells, KDS-5104 activated PPAR-α with an EC₅₀ of 100 ± 21 nM, comparable to OEA (120 ± 16 nM). The (S)-enantiomer (compound 4) was approximately three times less potent (EC₅₀ = 333 ± 27 nM). KDS-5104 did not activate PPAR-γ at 10 μM. [1] Molecular modeling studies suggested that the hydroxyl group of KDS-5104 interacts with Glu282, the amide CO interacts with the backbone NH of Tyr334, and the amide NH forms a hydrogen bond with the hydroxyl group of Thr279 within the PPAR-α ligand-binding domain. [1] |
| ln Vivo |
In free-feeding rats, intraperitoneal administration of KDS-5104 (5, 10, 20 mg/kg) dose-dependently prolonged feeding latency, with an ED₅₀ of 2.4 ± 1.8 mg/kg (n=18). Unlike OEA, KDS-5104 also caused a significant prolongation of both the first and second postmeal intervals (PMI), indicating a persistent satiety-inducing action. [1]
Oral administration of KDS-5104 (100 mg/kg) to free-feeding rats significantly reduced cumulative food intake for up to 4 hours following food presentation. In contrast, the same oral dose of OEA had no effect on food intake. Neither compound significantly affected locomotor activity. [1] |
| Enzyme Assay |
In Vitro Enzymatic Hydrolysis Assay: Test compounds (10 nmol) were incubated in 0.1 mL of Tris buffer (pH 8.2) containing mouse liver homogenate (0.7 mg protein) and 0.05% fatty acid-free bovine serum albumin for 0 to 60 minutes at 37°C. Reactions were stopped by protein precipitation with 0.25 mL of acetonitrile containing [²H₄]OEA as an internal standard. Samples were centrifuged, and supernatants were analyzed by LC-MS/MS. Separation was performed on a Synergi Polar-RP column using an isocratic mobile phase of acetonitrile/water/formic acid (80:20:0.1 v/v). Detection was performed using electrospray ionization in positive mode with multiple reaction monitoring. [1]
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| Cell Assay |
PPAR-α Transactivation Assay: HeLa cells stably transfected with a luciferase reporter plasmid and cotransfected with a plasmid containing the PPAR-α ligand-binding domain fused to the GAL4 DNA-binding domain were used. Cells were seeded in six-well plates and incubated for 7 hours in medium containing various concentrations of KDS-5104 or other test compounds. Luciferase activity in cell lysates was determined using a luciferase reporter assay system and a luminometer. [1]
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| Animal Protocol |
Rat Feeding Behavior Studies: Adult male Wistar rats (250-300 g) were housed under a 12-hour light/dark cycle (lights on at 4:45 AM) with ad libitum access to water and standard chow. For parenteral administration, KDS-5104 was dissolved in dimethyl sulfoxide/saline (70:30 v/v) and administered intraperitoneally (i.p.) at doses of 5, 10, or 20 mg/kg, 15 minutes before food presentation. For oral administration, the compound was suspended in water/carboxymethyl cellulose/Tween 80 (99.1:0.5:0.4 v/v) and administered by gavage at 100 mg/kg, 60 minutes before food presentation. Food intake and motor activity were recorded using a fully automated system. Meal pattern analysis was performed using a minimal postmeal interval of 10 minutes, assessing feeding latency, first meal size, and postmeal intervals. [1]
Pharmacokinetic Studies: For parenteral administration, OEA and KDS-5104 were dissolved in dimethyl sulfoxide/saline (70:30 v/v) and administered at 10 mg/kg i.p. to free-feeding rats. Tissues were collected at various time points, and lipids were extracted. OEA and KDS-5104 were quantified by LC-MS using electrospray ionization in positive mode, monitoring sodium adducts [M+Na]⁺. For oral administration, compounds were suspended in water/carboxymethyl cellulose/Tween 80 (99.1:0.5:0.4 v/v) and administered at 100 mg/kg by gavage. [1] |
| ADME/Pharmacokinetics |
After intraperitoneal administration (10 mg/kg) in rats, KDS-5104 reached maximal plasma concentration (Cmax) of 0.30 ± 0.03 μg/mL (approximately 2-fold higher than OEA) and had an area under the curve (AUC) of 43.64 μg•min/mL (approximately 5-fold greater than OEA). In the liver, Cmax was 18.72 ± 2.51 μg/g wet tissue (13-fold higher than OEA) and AUC was 1275.00 μg•min/g (23-fold greater than OEA). [1]
After oral administration (100 mg/kg), KDS-5104 showed significantly higher exposure than OEA. Plasma Cmax was 0.58 ± 0.06 μg/mL (vs. 0.07 ± 0.01 for OEA), and plasma AUC was 198.13 μg•min/mL (vs. 18.42 for OEA). Liver Cmax was 2.92 ± 0.79 μg/g wet tissue (vs. 0.16 ± 0.03 for OEA), and liver AUC was 674.12 μg•min/g (vs. 58.51 for OEA). [1] |
| Toxicity/Toxicokinetics |
No specific toxicity data for KDS-5104 are described in this article. The compound was well-tolerated at the administered doses (up to 20 mg/kg i.p. and 100 mg/kg oral) in rats, with no reported adverse effects on general behavior or locomotor activity. [1]
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| References |
[1]. Pharmacological characterization of hydrolysis-resistant analogs of oleoylethanolamide with potent anorexiant properties. J Pharmacol Exp Ther. 2006;318(2):563-570.
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| Additional Infomation |
KDS-5104 (AM-3102) is a hydrolysis-resistant analog of the endogenous PPAR-α ligand oleoylethanolamide (OEA). It is the (R)-methyl stereoisomer at the C-α position of the ethanolamine moiety. Unlike OEA, which is rapidly degraded by fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA), KDS-5104 resists enzymatic hydrolysis due to increased steric bulk around the amide bond. [1]
KDS-5104 retains high potency at PPAR-α (EC₅₀ = 100 nM) and produces prolonged anorexiant effects in rats after both parenteral and oral administration. Its improved pharmacokinetic profile (higher Cmax and AUC in plasma and liver) compared to OEA supports its potential as a tool for studying PPAR-α-mediated satiety and as a lead for anti-obesity drug development. [1] Molecular modeling suggested that the amide NH and CO groups and the terminal hydroxyl group of KDS-5104 are critical for PPAR-α interaction, consistent with the loss of activity observed for the N-methyl and reverse amide analogs. [1] AM3102 is a carboxyimide acid. |
| Molecular Formula |
C21H41NO2
|
|---|---|
| Molecular Weight |
339.56
|
| Exact Mass |
339.313
|
| Elemental Analysis |
C, 74.28; H, 12.17; N, 4.12; O, 9.42
|
| CAS # |
213182-22-0
|
| PubChem CID |
10569111
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| Appearance |
White to off-white solid powder
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| Density |
0.9±0.1 g/cm3
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| Boiling Point |
503.6±43.0 °C at 760 mmHg
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| Flash Point |
258.4±28.2 °C
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| Vapour Pressure |
0.0±2.9 mmHg at 25°C
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| Index of Refraction |
1.473
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| LogP |
6.71
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
24
|
| Complexity |
302
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CCCCCCCC/C=C\CCCCCCCC(=O)N[C@H](C)CO
|
| InChi Key |
IPVYNYWIRWMRHH-JPMGXVIASA-N
|
| InChi Code |
InChI=1S/C21H41NO2/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-21(24)22-20(2)19-23/h10-11,20,23H,3-9,12-19H2,1-2H3,(H,22,24)/b11-10-/t20-/m1/s1
|
| Chemical Name |
(Z)-N-[(2R)-1-hydroxypropan-2-yl]octadec-9-enamide
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| Synonyms |
AM-3102; KDS-5104; AM3102; KDS5104; AM 3102; KDS 5104; Methyl oleoylethanolamide
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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 (294.5 mM)
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9450 mL | 14.7249 mL | 29.4499 mL | |
| 5 mM | 0.5890 mL | 2.9450 mL | 5.8900 mL | |
| 10 mM | 0.2945 mL | 1.4725 mL | 2.9450 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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