ASB14780 is a 4-phenoxy analogue and an inhibitor (blocker/antagonist) of cytosolic phospholipase cPLA2α with IC50 of 20 nM.

Physicochemical Properties

Molecular Formula	C35H38N2O6
Molecular Weight	582.686029911041
Exact Mass	582.273
CAS #	1069046-00-9
PubChem CID	68519061
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	12
Heavy Atom Count	43
Complexity	702
Defined Atom Stereocenter Count	0
InChi Key	MBPXGBINIINSEU-UHFFFAOYSA-N
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
Chemical Name	2-amino-2-(hydroxymethyl)propane-1,3-diol;3-[1-(4-phenoxyphenyl)-3-(2-phenylethyl)indol-5-yl]propanoic acid
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 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)

Biological Activity

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].
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].
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.
References	[1]. Design, synthesis, and biological evaluation of 3-(1-Aryl-1H-indol-5-yl)propanoic acids as new indole-based cytosolic phospholipase A2α inhibitors. J Med Chem. 2014. 57(17):7244-62.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.