APX-115 free base

Cas：1270084-92-8

Product Information：

APX-115, also known as EWHA-18278, is a potent, orally active pan NADPH oxidase (Nox) inhibitor. APX-115 protects development of diabetic nephropathy in podocyte specific NOX5 transgenic mice. APX-115 might be a promising therapeutic agent for the treatment of DN because of its pan-NOX inhibitory activity, including its NOX5 inhibitory activity, and also owing to its anti-inflammatory effect.

Chemical Formula: C17H17N3O

Exact Mass: 279.1372

Molecular Weight: 279.343

Elemental Analysis: C, 73.10; H, 6.13; N, 15.04; O, 5.73

Synonym:

APX-115 free base

APX 115

APX115

EWHA-18278

EWHA 18278

EWHA18278

Chemical Name:

3-phenyl-4-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol

InChi Key: 

LQKQLKMTJOMCMJ-UHFFFAOYSA-N

InChi Code: InChI=1S/C17H17N3O/c1-2-8-14-16(13-9-4-3-5-10-13)19-20(17(14)21)15-11-6-7-12-18-15/h3-7,9-12,21H,2,8H2,1H3

Smiles Code:

OC1=C(CCC)C(C2=CC=CC=C2)=NN1C3=NC=CC=C3

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

In Vitro：

APX-115 free base (5 μM; 60 min) almost completely suppresses high glucose-induced proinflammatory and profibrotic molecule expression in the mouse podocyte cell line.

In the kidney, APX-115 free base attenuates Nox gene upregulation and protein expression while improving inflammatory and fibrotic processes.

In Vivo:

APX-115 free base (oral gavage; 60 mg/kg/day; for 12 weeks) significantly improves insulin resistance in diabetic mice.

APX-115 free base treatment decreases the urinary excretion of albumin and plasma creatinine levels.

References：

1. Lee ES, Kim HM, Lee SH, Ha KB, Bae YS, Lee SJ, Moon SH, Lee EY, Lee JH, Chung CH. APX-115, a pan-NADPH oxidase inhibitor, protects development of diabetic nephropathy in podocyte specific NOX5 transgenic mice. Free Radic Biol Med. 2020 Oct 2;161:92-101. doi: 10.1016/j.freeradbiomed.2020.09.024. Epub ahead of print. PMID: 33011273.

2. Chocry M, Leloup L. The NADPH Oxidase Family and Its Inhibitors. Antioxid Redox Signal. 2020 Aug 10;33(5):332-353. doi: 10.1089/ars.2019.7915. Epub 2020 Jan 23. PMID: 31826639.

3. Dorotea D, Kwon G, Lee JH, Saunders E, Bae YS, Moon SH, Lee SJ, Cha DR, Ha H. A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats. Pharmacology. 2018;102(3-4):180-189. doi: 10.1159/000491398. Epub 2018 Aug 10. PMID: 30099457.

4. Kwon G, Uddin MJ, Lee G, Jiang S, Cho A, Lee JH, Lee SR, Bae YS, Moon SH, Lee SJ, Cha DR, Ha H. 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. doi: 10.18632/oncotarget.18540. PMID: 29088780; PMCID: PMC5650335.

5. Cha JJ, Min HS, Kim KT, Kim JE, Ghee JY, Kim HW, Lee JE, Han JY, Lee G, Ha HJ, Bae YS, Lee SR, Moon SH, Lee SC, Kim G, Kang YS, Cha DR. 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. doi: 10.1038/labinvest.2017.2. Epub 2017 Feb 6. PMID: 28165467.

Products are for research use only. Not for human use.