APX-115 (Ewha-18278) is a potent, orally bioactive, non-selective Nox inhibitor (antagonist) with Kis of 1.08 μM, 0.57 μM and 0.63 μM for Nox1, Nox2 and Nox4 respectively. APX-115 effectively prevents kidney damage in diabetic mice.

Physicochemical Properties

Molecular Formula	C17H18CLN3O
Molecular Weight	315.797322750092
Exact Mass	315.113
CAS #	1395946-75-4
Related CAS #	APX-115 free base;1270084-92-8
PubChem CID	60172240
Appearance	Light yellow to yellow solid powder
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	22
Complexity	412
Defined Atom Stereocenter Count	0
SMILES	Cl.O=C1C(=C(C2C=CC=CC=2)NN1C1C=CC=CN=1)CCC
InChi Key	YEEIHSUMLNXRMI-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H17N3O.ClH/c1-2-8-14-16(13-9-4-3-5-10-13)19-20(17(14)21)15-11-6-7-12-18-15;/h3-7,9-12,19H,2,8H2,1H3;1H
Chemical Name	5-phenyl-4-propyl-2-pyridin-2-yl-1H-pyrazol-3-one;hydrochloride
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	Renal podocytes exposed to high potential for 60 minutes almost completely do not express pro-inflammatory and pro-fibrotic molecules when exposed to APX-115 (5 μM) [2]. APX-115 has the ability to enhance the fibrosis process in the kidney by inducing Nox gene upregulation and protein expression [2].
ln Vivo	In diabetic mice, APX-115 dramatically reduces insulin resistance [2]. Insulin and albumin concentrations are less effectively excreted when APX-115 is used [2].
Animal Protocol	Animal/Disease Models: Sixweeks old male diabetic db/db mice (C57BLKS/J-leprdb/leprdb) [2] Doses: 60 mg/kg Route of Administration: po (oral gavage); every day; for 12 weeks. Experimental Results: Significant improvement in diabetic symptoms Insulin resistance in rats.
References	[1]. A novel pan-Nox inhibitor, APX-115, protects kidney injury in streptozotocin-induced diabetic mice: possible role of peroxisomal and mitochondrial biogenesis. Oncotarget. 2017 Jun 16;8(43):74217-74232. [2]. APX-115, a first-in-class pan-NADPH oxidase (Nox) inhibitor, protects db/db mice from renal injury. Lab Invest. 2017 Apr;97(4):419-431.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~316.66 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.59 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 20.8 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: ≥ 2.08 mg/mL (6.59 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 20.8 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 3: ≥ 2.08 mg/mL (6.59 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 20.8 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	3.1666 mL	15.8328 mL	31.6656 mL
	5 mM	0.6333 mL	3.1666 mL	6.3331 mL
	10 mM	0.3167 mL	1.5833 mL	3.1666 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.