GLX351322
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MedKoo CAT#: 555343

CAS#: 835598-94-2

Description: GLX351322 is a NADPH oxidase 4 inhibitor. GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice. GLX351322 inhibits hydrogen peroxide production from tetracycline inducible NOX4-overexpressing cells with IC50 of 5 uM. Inhibition of NOX4 with GLX351322 attenuated AOH-induced retinal inflammation, cellular senescence, and apoptosis by inhibiting the activation of the redox-sensitive factor pathway mediated by ROS overproduction, thereby protecting retinal structure and function.

Chemical Structure

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GLX351322
CAS# 835598-94-2
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 555343
Name: GLX351322
CAS#: 835598-94-2
Chemical Formula: C21H25N3O5S
Exact Mass: 431.15
Molecular Weight: 431.510
Elemental Analysis: C, 58.45; H, 5.84; N, 9.74; O, 18.54; S, 7.43

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to ship
500mg USD 2950 Ready to ship
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Synonym: GLX351322; GLX-351322; GLX 351322

IUPAC/Chemical Name: Ethyl 2-[[2-[4-(furan-2-carbonyl)piperazin-1-yl]acetyl]amino]-5,6-dihydro-4H-cyclopenta-[b]thiophene-3-carboxylate

InChi Key: KEVHLTCEMHIJTQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H25N3O5S/c1-2-28-21(27)18-14-5-3-7-16(14)30-19(18)22-17(25)13-23-8-10-24(11-9-23)20(26)15-6-4-12-29-15/h4,6,12H,2-3,5,7-11,13H2,1H3,(H,22,25)

SMILES Code: O=C(C1=C(NC(CN2CCN(C(C3=CC=CO3)=O)CC2)=O)SC4=C1CCC4)OCC

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: 2934.99.03.00

More Info: In type 2 diabetes, it has been proposed that pancreatic beta-cell dysfunction is promoted by oxidative stress caused by NADPH oxidase (NOX) overactivity. Five different NOX enzymes (NOX1-5) have been characterized, among which NOX1 and NOX2 have been proposed to negatively affect beta-cells, but the putative role of NOX4 in type 2 diabetes-associated beta-cell dysfunction and glucose intolerance is largely unknown

Biological target: GLX351322 is an inhibitor of NADPH oxidase 4 (Nox4), and inhibits hydrogen peroxide production from NOX4-overexpressing cells with an IC50 of 5 μM.
In vitro activity: oeUSP7 cells and vector control cells were treated with a NOX4 inhibitor (GLX351322, 10 μM) to study NOX4’s role in USP7 regulation. Flow cytometry assay showed that inhibition of NOX4 by GLX351322 significantly decreased oeUSP7-induced pyroptosis and ROS production (Figures 5A,B). This study also found that oeUSP7-increased IL-1β and IL-18 were abolished by the inhibition of NOX4 with GLX351322 (Figure 5C). Western blotting results indicated that oeUSP7 resulted in increased expressions of NLRP3, GSDMD-N, active caspase-1, and pro-caspase-1, which was dramatically suppressed by GLX351322 (Figure 5D). These data suggest that USP7 overexpression promotes NLRP3 inflammasome activation and pyroptosis by increasing NOX4. Reference: Front Pharmacol. 2021 Jan 29;11:617270. https://pubmed.ncbi.nlm.nih.gov/33584299/
In vivo activity: To investigate the effect of hypoxia on NOX2 and NOX4 expression and its role in ANP secretion, a series of experiments were performed using isolated perfused beating rat atria. The results showed that hypoxia significantly upregulated the expression of NOX4 but not NOX2 (p < 0.05 vs. control; Fig. 2A and B), which was completely blocked by the ETRA and ETRB antagonists BQ123 and BQ788, respectively (p < 0.05 vs. hypoxia; Fig. 2B). In addition, hypoxia-induced ANP secretion was substantially attenuated by the NOX4 antagonist GLX351322 (p < 0.05 vs. control and hypoxia, respectively; Fig. 2C). The hypoxia-induced atrial dynamics were shifted to a rightward slightly by GLX351322, but it failed to significantly modulate the inhibitory effect of hypoxia on atrial dynamics (p < 0.05 vs. control; Fig. 2D). These results indicate that NOX4 regulated by endogenous ET-1 is involved in the regulation of ANP secretion in beating rat atria under hypoxic conditions. Reference: Korean J Physiol Pharmacol. 2021 Mar 1; 25(2): 159–166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893495/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 46.35
DMF 1.0 2.32
DMF:PBS (pH 7.2) (1:2) 0.3 0.76
Ethanol 4.0 9.27

Preparing Stock Solutions

The following data is based on the product molecular weight 431.51 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wu CZ, Li X, Hong L, Han ZN, Liu Y, Wei CX, Cui X. NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria. Korean J Physiol Pharmacol. 2021 Mar 1;25(2):159-166. doi: 10.4196/kjpp.2021.25.2.159. PMID: 33602886; PMCID: PMC7893495. 2. Anvari E, Wikström P, Walum E, Welsh N. The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice. Free Radic Res. 2015;49(11):1308-18. doi: 10.3109/10715762.2015.1067697. Epub 2015 Jul 30. PMID: 26118714. 3. Liu G, Liu Q, Yan B, Zhu Z, Xu Y. USP7 Inhibition Alleviates H2O2-Induced Injury in Chondrocytes via Inhibiting NOX4/NLRP3 Pathway. Front Pharmacol. 2021 Jan 29;11:617270. doi: 10.3389/fphar.2020.617270. PMID: 33584299; PMCID: PMC7879569.
In vitro protocol: 1. Liu G, Liu Q, Yan B, Zhu Z, Xu Y. USP7 Inhibition Alleviates H2O2-Induced Injury in Chondrocytes via Inhibiting NOX4/NLRP3 Pathway. Front Pharmacol. 2021 Jan 29;11:617270. doi: 10.3389/fphar.2020.617270. PMID: 33584299; PMCID: PMC7879569.
In vivo protocol: 1. Wu CZ, Li X, Hong L, Han ZN, Liu Y, Wei CX, Cui X. NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria. Korean J Physiol Pharmacol. 2021 Mar 1;25(2):159-166. doi: 10.4196/kjpp.2021.25.2.159. PMID: 33602886; PMCID: PMC7893495. 2. Anvari E, Wikström P, Walum E, Welsh N. The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice. Free Radic Res. 2015;49(11):1308-18. doi: 10.3109/10715762.2015.1067697. Epub 2015 Jul 30. PMID: 26118714.

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1: Huang YF, Wang G, Ding L, Bai ZR, Leng Y, Tian JW, Zhang JZ, Li YQ, Ahmad, Qin YH, Li X, Qi X. Lactate-upregulated NADPH-dependent NOX4 expression via HCAR1/PI3K pathway contributes to ROS-induced osteoarthritis chondrocyte damage. Redox Biol. 2023 Sep 4;67:102867. doi: 10.1016/j.redox.2023.102867. Epub ahead of print. PMID: 37688977; PMCID: PMC10498433.


2: Liao J, Peng B, Huang G, Diao C, Qin Y, Hong Y, Lin J, Lin Y, Jiang L, Tang N, Tang F, Liang J, Zhang J, Yan Y, Chen Q, Zhou Z, Shen C, Huang W, Huang K, Lan Q, Cui L, Zhong H, Xu F, Li M, Wei Y, Lu P, Zhang M. Inhibition of NOX4 with GLX351322 alleviates acute ocular hypertension-induced retinal inflammation and injury by suppressing ROS mediated redox-sensitive factors activation. Biomed Pharmacother. 2023 Sep;165:115052. doi: 10.1016/j.biopha.2023.115052. Epub 2023 Jul 1. PMID: 37399715.


3: Li H, Ren J, Cui H, Wang D, Zhao R, Liu X, Tian S, Wang J, Zhang J, Li P, Thorne RF, Duan S. Dexamethasone Induces Senescence-Associated Changes in Trabecular Meshwork Cells by Increasing ROS Levels Via the TGFβ/Smad3-NOX4 Axis. Cell Transplant. 2023 Jan-Dec;32:9636897231177356. doi: 10.1177/09636897231177356. PMID: 37265069; PMCID: PMC10272683.


4: Li H, Cui H, Ren J, Wang D, Zhao R, Zhu S, Liu S, Liu X, Tian S, Zhang Y, Zhao P, Li P, Thorne RF, Duan S. Elevated Angiotensin-II Levels Contribute to the Pathogenesis of Open-Angle Glaucoma Via Inducing the Expression of Fibrosis- Related Genes in Trabecular Meshwork Cells Through a ROS/NOX4/SMAD3 Axis. Cell Transplant. 2023 Jan-Dec;32:9636897231162526. doi: 10.1177/09636897231162526. PMID: 36999649; PMCID: PMC10068978.


5: Xu J, Yu Z, Li W. Kaempferol inhibits airway inflammation induced by allergic asthma through NOX4-Mediated autophagy. Hum Exp Toxicol. 2023 Jan- Dec;42:9603271231154227. doi: 10.1177/09603271231154227. PMID: 36803065.


6: Zhen J, Chen X, Mao Y, Xie X, Chen X, Xu W, Zhang S. GLX351322, a Novel NADPH Oxidase 4 Inhibitor, Attenuates TMJ Osteoarthritis by Inhibiting the ROS/MAPK/NF-κB Signaling Pathways. Oxid Med Cell Longev. 2023 Jan 30;2023:1952348. doi: 10.1155/2023/1952348. PMID: 36756301; PMCID: PMC9902131.


7: Jiang H, Li F, Cai L, Chen Q. Role of the TSPO-NOX4 axis in angiogenesis in glioblastoma. Front Pharmacol. 2022 Oct 7;13:1001588. doi: 10.3389/fphar.2022.1001588. PMID: 36278207; PMCID: PMC9585329.


8: Mourmoura E, Papathanasiou I, Trachana V, Konteles V, Tsoumpou A, Goutas A, Papageorgiou AA, Stefanou N, Tsezou A. Leptin-depended NLRP3 inflammasome activation in osteoarthritic chondrocytes is mediated by ROS. Mech Ageing Dev. 2022 Dec;208:111730. doi: 10.1016/j.mad.2022.111730. Epub 2022 Sep 7. PMID: 36087742.


9: Thapa J, Yoshiiri G, Ito K, Okubo T, Nakamura S, Furuta Y, Higashi H, Yamaguchi H. Chlamydia trachomatis Requires Functional Host-Cell Mitochondria and NADPH Oxidase 4/p38MAPK Signaling for Growth in Normoxia. Front Cell Infect Microbiol. 2022 May 26;12:902492. doi: 10.3389/fcimb.2022.902492. PMID: 35719337; PMCID: PMC9199516.


10: Li Q, Hua X, Li L, Zhou X, Tian Y, Deng Y, Zhang M, Yuan X, Chi W. AIP1 suppresses neovascularization by inhibiting the NOX4-induced NLRP3/NLRP6 imbalance in a murine corneal alkali burn model. Cell Commun Signal. 2022 May 6;20(1):59. doi: 10.1186/s12964-022-00877-5. PMID: 35524333; PMCID: PMC9074213.


11: Tang P, Sheng J, Peng X, Zhang R, Xu T, Hu J, Kang Y, Wu B, Dang H. Targeting NOX4 disrupts the resistance of papillary thyroid carcinoma to chemotherapeutic drugs and lenvatinib. Cell Death Discov. 2022 Apr 8;8(1):177. doi: 10.1038/s41420-022-00994-7. PMID: 35396551; PMCID: PMC8990679.


12: Miyashita-Ishiwata M, El Sabeh M, Reschke LD, Afrin S, Borahay MA. Hypoxia induces proliferation via NOX4-Mediated oxidative stress and TGF-β3 signaling in uterine leiomyoma cells. Free Radic Res. 2022 Feb;56(2):163-172. doi: 10.1080/10715762.2022.2061967. Epub 2022 Apr 15. PMID: 35377824; PMCID: PMC9863770.


13: Li ZY, Liu Y, Wang YY, Li X, Han ZN, Hong L, Li YS, Cui X. NOX4 stimulates ANF secretion via activation of the Sirt1/Nrf2/ATF3/4 axis in hypoxic beating rat atria. Mol Med Rep. 2022 Mar;25(3):84. doi: 10.3892/mmr.2022.12600. Epub 2022 Jan 14. PMID: 35029280; PMCID: PMC8809118.


14: Wu CZ, Li X, Hong L, Han ZN, Liu Y, Wei CX, Cui X. NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria. Korean J Physiol Pharmacol. 2021 Mar 1;25(2):159-166. doi: 10.4196/kjpp.2021.25.2.159. PMID: 33602886; PMCID: PMC7893495.


15: Tao W, Yu L, Shu S, Liu Y, Zhuang Z, Xu S, Bao X, Gu Y, Cai F, Song W, Xu Y, Zhu X. miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer's Disease. Mol Ther. 2021 Jan 6;29(1):396-408. doi: 10.1016/j.ymthe.2020.09.006. Epub 2020 Sep 5. PMID: 32950103; PMCID: PMC7791017.


16: Lee HR, Yoo SJ, Kim J, Yoo IS, Park CK, Kang SW. The effect of nicotinamide adenine dinucleotide phosphate oxidase 4 on migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis. Arthritis Res Ther. 2020 May 15;22(1):116. doi: 10.1186/s13075-020-02204-0. PMID: 32414400; PMCID: PMC7227051.


17: Wang X, Elksnis A, Wikström P, Walum E, Welsh N, Carlsson PO. The novel NADPH oxidase 4 selective inhibitor GLX7013114 counteracts human islet cell death in vitro. PLoS One. 2018 Sep 28;13(9):e0204271. doi: 10.1371/journal.pone.0204271. PMID: 30265686; PMCID: PMC6161897.


18: Anvari E, Wikström P, Walum E, Welsh N. The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice. Free Radic Res. 2015;49(11):1308-18. doi: 10.3109/10715762.2015.1067697. Epub 2015 Jul 30. PMID: 26118714.