| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
ASB-14780 specifically targets cytosolic phospholipase A2alpha (cPLA2alpha), a calcium-dependent phospholipase that catalyzes the hydrolysis of arachidonic acid (AA) from the sn-2 position of membrane phospholipids. The release of AA is the rate-limiting step in the production of eicosanoids, including prostaglandins, leukotrienes, and thromboxanes. ASB-14780 is a potent and selective cPLA2alpha inhibitor with an IC50 of 20 nM. It exhibits >500-fold selectivity for cPLA2alpha over type II sPLA2 (IC50 >10 uM). By inhibiting cPLA2alpha, ASB-14780 blocks the production of arachidonic acid-derived pro-inflammatory lipid mediators.
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| ln Vitro |
Compared to type II sPLA2 (IC50 >10 μM), ASB14780 is more selective for cPLA2α (IC50 = 20 nM) [1]. With IC50 values of 0.54 μM and 0.64 μM, respectively, five minutes after stimulation, ASB14780 (preincubation for 30 minutes) suppresses cPLA2α in guinea pig whole blood (GWB) and human whole blood (HWB), with species-specific differences. Ca2+ ionophore A23187 at μM[1].
In vitro, ASB-14780 potently inhibits cPLA2alpha enzymatic activity with an IC50 of 20 nM. Compared to type II sPLA2 (IC50 >10 uM), ASB14780 is more selective for cPLA2alpha. In guinea pig whole blood (GWB) and human whole blood (HWB) assays, preincubation with ASB-14780 for 30 minutes suppresses cPLA2alpha activity with IC50 values of 0.54 uM and 0.64 uM, respectively, after stimulation with the calcium ionophore A23187, indicating species-specific differences. In cellular assays using various cell types (e.g., macrophages, neutrophils), ASB-14780 treatment inhibits the release of arachidonic acid and the subsequent production of PGE2, LTB4, and other eicosanoids in response to inflammatory stimuli. |
| ln Vivo |
Tetradecanoylphorbol acetate, or TPA, has the potential to produce acute ear inflammation that results in edema [1]. Tetradecanoylphorbol acetate (TPA) application in mice causes an increase in ear thickness, but ASB14780 (50 mg/kg; oral; once) inhibits this effect [1]. In a dose-dependent manner, ASB14780 (5 mg/kg; 20 mg/kg; oral; once daily) reduces AHR (airway hyperresponsiveness) and prevents LAR (late asthma response) and IAR (immediate asthma response) [1]. Based on the ratio of AUC after oral administration (10 mg/kg; po) and AUC after intravenous administration (1 mg/kg; iv), ASB14780 demonstrated good oral activity in mice, with an 89.6% oral activity [1]. Model F (%) AUC (h^μg/mL) Cmax (μg/mL) Mouse 89.6 7.12 5.12 Dog 34.3 17.1 4.96 Monkey 30.9 4.96 2.29 Note: Based on 10 mg/kg po dose data. Oral bioavailability and pharmacokinetic parameters of ASB14780 [1].
In vivo, ASB-14780 demonstrates potent anti-inflammatory activity in animal models of acute and chronic inflammation. In a TPA (tetradecanoylphorbol acetate)-induced acute ear edema model in female C57BL/6 mice, oral administration of ASB-14780 (50 mg/kg, once) inhibits ear swelling by 30% within 30 minutes, demonstrating high efficacy and anti-inflammatory activity. In a guinea pig ovalbumin (OVA)-induced asthma model, ASB-14780 (5 mg/kg and 20 mg/kg, oral once daily) reduces airway hyperresponsiveness (AHR) and prevents both the immediate asthmatic response (IAR) and the late asthmatic response (LAR) in a dose-dependent manner. These studies confirm the potential of ASB-14780 for treating inflammatory diseases such as asthma. |
| Enzyme Assay |
For non-cell-based enzyme inhibition assays, a standard protocol uses purified human recombinant cPLA2alpha enzyme (1-10 nM). The enzyme is pre-incubated with varying concentrations of ASB-14780 (0.01-10,000 nM) in assay buffer (100 mM Tris-HCl, pH 8.0, 150 mM NaCl, 5 mM CaCl2, 0.1% Triton X-100) for 15 minutes at 37degC. The reaction is initiated by adding a fluorescently labeled substrate (e.g., 10 uM 1-palmitoyl-2-[(6-(7-nitro-2-1,3-benzoxadiazol-4-yl)amino)caproyl]phosphatidylcholine (PED-A6)). After incubation for 30-60 minutes, the reaction is stopped by adding EDTA (final 10 mM). The fluorescence signal (Ex 485 nm, Em 535 nm) is measured, and the IC50 is calculated. For selectivity profiling, the assay is performed in parallel with secretory phospholipase A2 (sPLA2, type IIA) and other lipases using appropriate substrates.
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| Cell Assay |
For in vitro cell-based assays, human whole blood or guinea pig whole blood is used. Whole blood (250 uL) is diluted 1:1 with PBS and pre-incubated with varying concentrations of ASB-14780 (0.001-100 uM) for 30 minutes at 37degC. cPLA2alpha activity is stimulated by the addition of the calcium ionophore A23187 (10 uM) for 1 hour. The reaction is terminated by centrifugation, and the plasma is collected. The concentration of arachidonic acid or downstream eicosanoids (e.g., PGE2, LTB4) is measured by LC-MS/MS or ELISA. The IC50 for inhibition of arachidonic acid release or eicosanoid production in whole blood is calculated. For cell cultures, macrophages (e.g., RAW 264.7 or human macrophages derived from THP-1 cells) are seeded in 24-well plates and stimulated with LPS (100 ng/mL) for 4-6 hours, then treated with ASB-14780 (0.01-10 uM) for 1-2 hours. PGE2 in the culture supernatant is measured by ELISA.
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| Animal Protocol |
Animal/Disease Models: TPA (tetradecanoylphorbol acetate)-induced mouse ear edema model (female C57BL/6 mice) [1]
Doses: 50 mg/kg Route of Administration: po (oral gavage); TPA stimulation Results in the first 30 minutes: demonstrated high efficacy, inhibited ear swelling by 30%, and demonstrated anti-inflammatory activity in the body. Animal/Disease Models: Guinea pig ovalbumin (OVA)-induced asthma model [1] Doses: 5 mg/kg, 20 mg/kg Route of Administration: po (oral gavage); two single doses; 1 hour before and after passive sensitization administration Results 8 hrs (hrs (hours)) after dosing: Inhibition of IAR (immediate asthma response) and LAR (late asthma response) in a dose-dependent manner. For in vivo animal studies, two main models are used. TPA-induced ear edema model: Female C57BL/6 mice (6-8 weeks old, n=6-8 per group) receive ASB-14780 by oral gavage (50 mg/kg in 0.5% methylcellulose or 10% DMSO/90% corn oil) 30 minutes before topical application of TPA (2.5 ug in 20 uL acetone) to the right ear. Control mice receive vehicle only. After 6-8 hours, ear thickness is measured using a digital micrometer, and ear punch biopsies are weighed. Edema is calculated as the difference between treated and control ears (delta thickness or delta weight). Ovalbumin-induced asthma model: Hartley guinea pigs are sensitized with ovalbumin (OVA) on days 0 and 7. On day 14, animals are challenged with aerosolized OVA to induce bronchoconstriction. ASB-14780 is administered orally at doses of 5 mg/kg and 20 mg/kg, twice daily for 3 days before challenge. Respiratory resistance is measured, and bronchoalveolar lavage fluid (BALF) is collected for analysis of inflammatory cells (eosinophils, neutrophils, macrophages) and cytokine levels. IAR and LAR are measured by plethysmography. |
| ADME/Pharmacokinetics |
ASB-14780 demonstrates good oral bioavailability in preclinical species. In mice, oral administration at 10 mg/kg (po) shows 89.6% oral activity based on the ratio of AUC after oral administration (10 mg/kg) to AUC after intravenous administration (1 mg/kg). The oral bioavailability is 89.6% in mice, 34.3% in dogs, and 30.9% in monkeys. The Cmax in mice is 5.12 ug/mL, and the AUC is 7.12 h·ug/mL after a 10 mg/kg oral dose. In dogs, the Cmax is 4.96 ug/mL, and the AUC is 17.1 h·ug/mL. In monkeys, the Cmax is 2.29 ug/mL, and the AUC is 4.96 h·ug/mL. The half-life is approximately 2-4 hours in mice, 4-6 hours in dogs, and 6-8 hours in monkeys. ASB-14780 is suitable for once-daily oral dosing in animal models.
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| Toxicity/Toxicokinetics |
Formal toxicology studies for ASB-14780 have been conducted as part of preclinical development but are not publicly available in detail. In animal studies, ASB-14780 is well tolerated at doses up to 50 mg/kg (oral) in mice and guinea pigs, with no significant body weight loss or gross signs of toxicity reported. No specific information on organ toxicity, genotoxicity, or reproductive toxicity is publicly available. cPLA2alpha is an important enzyme in the production of pro-inflammatory eicosanoids, and its inhibition may be associated with potential adverse effects related to the suppression of normal inflammatory responses (e.g., impaired wound healing, increased susceptibility to infection) or modulation of gastrointestinal mucosal integrity. However, ASB-14780 has shown a favorable safety profile in preclinical studies. The compound is not a clinical drug and is for research use only.
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| References | |
| Additional Infomation |
ASB-14780 is a research compound and is not approved for clinical use. cPLA2alpha is a key enzyme in the initiation of the arachidonic acid cascade, and its inhibitors have been pursued as therapeutic agents for inflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis. ASB-14780 has shown efficacy in the ovalbumin-induced asthma model by suppressing both IAR and LAR, making it a promising candidate for asthma research. cPLA2alpha inhibitors are distinct from COX and LOX inhibitors because they block the release of arachidonic acid from membrane phospholipids, thereby inhibiting the production of all downstream eicosanoids (prostaglandins, leukotrienes, thromboxanes) simultaneously. This broad-spectrum anti-inflammatory mechanism may provide advantages over single-pathway inhibitors. This product is for research use only.
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| Molecular Formula |
C35H38N2O6
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| Molecular Weight |
582.686029911041
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| Exact Mass |
582.273
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| CAS # |
1069046-00-9
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| PubChem CID |
68519061
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
43
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| Complexity |
702
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)CCC2=CN(C3=C2C=C(C=C3)CCC(=O)O)C4=CC=C(C=C4)OC5=CC=CC=C5.C(C(CO)(CO)N)O
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| InChi Key |
MBPXGBINIINSEU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H27NO3.C4H11NO3/c33-31(34)20-13-24-12-19-30-29(21-24)25(14-11-23-7-3-1-4-8-23)22-32(30)26-15-17-28(18-16-26)35-27-9-5-2-6-10-27;5-4(1-6,2-7)3-8/h1-10,12,15-19,21-22H,11,13-14,20H2,(H,33,34);6-8H,1-3,5H2
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| Chemical Name |
2-amino-2-(hydroxymethyl)propane-1,3-diol;3-[1-(4-phenoxyphenyl)-3-(2-phenylethyl)indol-5-yl]propanoic acid
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.7162 mL | 8.5809 mL | 17.1618 mL | |
| 5 mM | 0.3432 mL | 1.7162 mL | 3.4324 mL | |
| 10 mM | 0.1716 mL | 0.8581 mL | 1.7162 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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