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MedKoo Cat#: 562750 | Name: GKT136901
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

GKT136901 is a dual inhibitor of NADPH oxidase 1 (NOX1) and NOX4 (Kis = 160 and 165 nM, respectively). It is selective for NOX1 and NOX4 over NOX2 and xanthine oxidase (Kis = 1,530 and >30,000 nM, respectively), as well as over a panel of 18 enzymes and ion channels at 10 µM. GKT136901 (0.1, 1, and 10 µM) scavenges peroxynitrite radicals, as well as prevents the nitration and dimerization of α-synuclein, in cell-free assays. It prevents peroxynitrite-induced cell death of differentiated LUHMES cells when used at a concentration of 10 µM.

Chemical Structure

GKT136901
GKT136901
CAS#955272-06-7

Theoretical Analysis

MedKoo Cat#: 562750

Name: GKT136901

CAS#: 955272-06-7

Chemical Formula: C19H15ClN4O2

Exact Mass: 366.0884

Molecular Weight: 366.81

Elemental Analysis: C, 62.22; H, 4.12; Cl, 9.66; N, 15.27; O, 8.72

Price and Availability

Size Price Availability Quantity
50mg USD 350.00 2 Weeks
100mg USD 550.00 2 Weeks
250mg USD 950.00 2 Weeks
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Related CAS #
No Data
Synonym
GKT136901; GKT-136901; GKT 136901; NOX Inhibitor IV;
IUPAC/Chemical Name
2-(2-Chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-dione
InChi Key
DNKYHHFCPXKFIY-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H15ClN4O2/c1-12-18-15(10-17(25)23(12)11-13-6-4-5-9-21-13)22-24(19(18)26)16-8-3-2-7-14(16)20/h2-10,22H,11H2,1H3
SMILES Code
O=C1N(C2=CC=CC=C2Cl)NC(C1=C(C)N3CC4=NC=CC=C4)=CC3=O
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
>2 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
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
GKT136901 is a potent, selective and orally active inhibitor of NADPH oxidase (NOX1/4), with Kis of 160 and 165 nM, respectively.
In vitro activity:
GKT136901 impaired cell viability of these cells (Fig, 2A). On the basis of these results, HBMECs were pretreated with 10 μM of GKT136901 for 2 h prior to METH treatment. As expected, GKT136901 significantly abolished ROS generation stimulated by METH treatment (Fig. 2B, C). In addition, GKT136901 also eliminated METH-induced decline in intracellular GSH level in HBMECs (Fig. 2D), indicating that GKT136901 reduces METH-induced oxidative stress. Reference: Life Sci. 2020 Sep 1;256:117917. https://pubmed.ncbi.nlm.nih.gov/32525001/
In vivo activity:
GKT136901, a specific dual inhibitor of Nox1 and Nox4, prevented these events in diabetic Wistar Kyoto rats and spontaneously hypertensive rats. Retinal neovascularization does not develop in diabetic rodents, and therefore, the oxygen-induced retinopathy model is used to evaluate this pathology. Reference: Hypertension. 2020 Apr;75(4):1091-1101. https://pubmed.ncbi.nlm.nih.gov/32114846/
Solvent mg/mL mM
Solubility
DMF 25.0 68.16
DMSO 30.0 81.79
DMSO:PBS (pH 7.2) (1:6) 0.1 0.38
Ethanol 1.0 2.73
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 366.81 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. Hwang JS, Cha EH, Ha E, Park B, Seo JH. GKT136901 protects primary human brain microvascular endothelial cells against methamphetamine-induced blood-brain barrier dysfunction. Life Sci. 2020 Sep 1;256:117917. doi: 10.1016/j.lfs.2020.117917. Epub 2020 Jun 7. PMID: 32525001. 2. Schildknecht S, Weber A, Gerding HR, Pape R, Robotta M, Drescher M, Marquardt A, Daiber A, Ferger B, Leist M. The NOX1/4 inhibitor GKT136901 as selective and direct scavenger of peroxynitrite. Curr Med Chem. 2014;21(3):365-76. doi: 10.2174/09298673113209990179. PMID: 23848532. 3. Deliyanti D, Alrashdi SF, Touyz RM, Kennedy CR, Jha JC, Cooper ME, Jandeleit-Dahm KA, Wilkinson-Berka JL. Nox (NADPH Oxidase) 1, Nox4, and Nox5 Promote Vascular Permeability and Neovascularization in Retinopathy. Hypertension. 2020 Apr;75(4):1091-1101. doi: 10.1161/HYPERTENSIONAHA.119.14100. Epub 2020 Mar 2. PMID: 32114846. 4. Sedeek M, Gutsol A, Montezano AC, Burger D, Nguyen Dinh Cat A, Kennedy CR, Burns KD, Cooper ME, Jandeleit-Dahm K, Page P, Szyndralewiez C, Heitz F, Hebert RL, Touyz RM. Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes. Clin Sci (Lond). 2013 Feb;124(3):191-202. doi: 10.1042/CS20120330. PMID: 22920224.
In vitro protocol:
1. Hwang JS, Cha EH, Ha E, Park B, Seo JH. GKT136901 protects primary human brain microvascular endothelial cells against methamphetamine-induced blood-brain barrier dysfunction. Life Sci. 2020 Sep 1;256:117917. doi: 10.1016/j.lfs.2020.117917. Epub 2020 Jun 7. PMID: 32525001. 2. Schildknecht S, Weber A, Gerding HR, Pape R, Robotta M, Drescher M, Marquardt A, Daiber A, Ferger B, Leist M. The NOX1/4 inhibitor GKT136901 as selective and direct scavenger of peroxynitrite. Curr Med Chem. 2014;21(3):365-76. doi: 10.2174/09298673113209990179. PMID: 23848532.
In vivo protocol:
1. Deliyanti D, Alrashdi SF, Touyz RM, Kennedy CR, Jha JC, Cooper ME, Jandeleit-Dahm KA, Wilkinson-Berka JL. Nox (NADPH Oxidase) 1, Nox4, and Nox5 Promote Vascular Permeability and Neovascularization in Retinopathy. Hypertension. 2020 Apr;75(4):1091-1101. doi: 10.1161/HYPERTENSIONAHA.119.14100. Epub 2020 Mar 2. PMID: 32114846. 2. Sedeek M, Gutsol A, Montezano AC, Burger D, Nguyen Dinh Cat A, Kennedy CR, Burns KD, Cooper ME, Jandeleit-Dahm K, Page P, Szyndralewiez C, Heitz F, Hebert RL, Touyz RM. Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes. Clin Sci (Lond). 2013 Feb;124(3):191-202. doi: 10.1042/CS20120330. PMID: 22920224.
1: Miguel-Jiménez S, Pina-Beltrán B, Gimeno-Martos S, Carvajal-Serna M, Casao A, Pérez-Pe R. NADPH Oxidase 5 and Melatonin: Involvement in Ram Sperm Capacitation. Front Cell Dev Biol. 2021 May 7;9:655794. doi: 10.3389/fcell.2021.655794. PMID: 34026754; PMCID: PMC8138477. 2: Hwang JS, Cha EH, Ha E, Park B, Seo JH. GKT136901 protects primary human brain microvascular endothelial cells against methamphetamine-induced blood- brain barrier dysfunction. Life Sci. 2020 Sep 1;256:117917. doi: 10.1016/j.lfs.2020.117917. Epub 2020 Jun 7. PMID: 32525001. 3: Uchiyama N, Yukawa T, Dragan YP, Wagoner MP, Naven RT. New phenotypic cytotoxicity assay for ROS-inducing compounds using rat renal epithelial cells. Toxicol Lett. 2020 Oct 1;331:227-234. doi: 10.1016/j.toxlet.2020.06.005. Epub 2020 Jun 6. PMID: 32522578. 4: Deliyanti D, Alrashdi SF, Touyz RM, Kennedy CR, Jha JC, Cooper ME, Jandeleit- Dahm KA, Wilkinson-Berka JL. Nox (NADPH Oxidase) 1, Nox4, and Nox5 Promote Vascular Permeability and Neovascularization in Retinopathy. Hypertension. 2020 Apr;75(4):1091-1101. doi: 10.1161/HYPERTENSIONAHA.119.14100. Epub 2020 Mar 2. PMID: 32114846. 5: Dao VT, Elbatreek MH, Altenhöfer S, Casas AI, Pachado MP, Neullens CT, Knaus UG, Schmidt HHHW. Isoform-selective NADPH oxidase inhibitor panel for pharmacological target validation. Free Radic Biol Med. 2020 Feb 20;148:60-69. doi: 10.1016/j.freeradbiomed.2019.12.038. Epub 2019 Dec 25. PMID: 31883469. 6: Lu WJ, Li JY, Chen RJ, Huang LT, Lee TY, Lin KH. VAS2870 and VAS3947 attenuate platelet activation and thrombus formation via a NOX-independent pathway downstream of PKC. Sci Rep. 2019 Dec 11;9(1):18852. doi: 10.1038/s41598-019-55189-5. PMID: 31827142; PMCID: PMC6906488. 7: Yang N, Gonzalez-Vicente A, Garvin JL. Angiotensin II-induced superoxide and decreased glutathione in proximal tubules: effect of dietary fructose. Am J Physiol Renal Physiol. 2020 Jan 1;318(1):F183-F192. doi: 10.1152/ajprenal.00462.2019. Epub 2019 Nov 25. PMID: 31760771; PMCID: PMC6985822. 8: Augsburger F, Filippova A, Rasti D, Seredenina T, Lam M, Maghzal G, Mahiout Z, Jansen-Dürr P, Knaus UG, Doroshow J, Stocker R, Krause KH, Jaquet V. Pharmacological characterization of the seven human NOX isoforms and their inhibitors. Redox Biol. 2019 Sep;26:101272. doi: 10.1016/j.redox.2019.101272. Epub 2019 Jul 11. PMID: 31330481; PMCID: PMC6658998. 9: Casas AI, Hassan AA, Larsen SJ, Gomez-Rangel V, Elbatreek M, Kleikers PWM, Guney E, Egea J, López MG, Baumbach J, Schmidt HHHW. From single drug targets to synergistic network pharmacology in ischemic stroke. Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7129-7136. doi: 10.1073/pnas.1820799116. Epub 2019 Mar 20. PMID: 30894481; PMCID: PMC6452748. 10: Wong HS, Benoit B, Brand MD. Mitochondrial and cytosolic sources of hydrogen peroxide in resting C2C12 myoblasts. Free Radic Biol Med. 2019 Jan;130:140-150. doi: 10.1016/j.freeradbiomed.2018.10.448. Epub 2018 Oct 31. PMID: 30389498. 11: Yi J, Yuan Y, Zheng J, Zhao T. Hydrogen sulfide alleviates uranium-induced rat hepatocyte cytotoxicity via inhibiting Nox4/ROS/p38 MAPK pathway. J Biochem Mol Toxicol. 2019 Mar;33(3):e22255. doi: 10.1002/jbt.22255. Epub 2018 Oct 28. PMID: 30368988. 12: Muñoz M, Martínez MP, López-Oliva ME, Rodríguez C, Corbacho C, Carballido J, García-Sacristán A, Hernández M, Rivera L, Sáenz-Medina J, Prieto D. Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium- dependent vasodilatation of intrarenal arteries. Redox Biol. 2018 Oct;19:92-104. doi: 10.1016/j.redox.2018.08.004. Epub 2018 Aug 7. PMID: 30125808; PMCID: PMC6105769. 13: Appukuttan B, Ma Y, Stempel A, Ashander LM, Deliyanti D, Wilkinson-Berka JL, Smith JR. Effect of NADPH oxidase 1 and 4 blockade in activated human retinal endothelial cells. Clin Exp Ophthalmol. 2018 Aug;46(6):652-660. doi: 10.1111/ceo.13155. Epub 2018 Feb 23. PMID: 29360265. 14: Casas AI, Geuss E, Kleikers PWM, Mencl S, Herrmann AM, Buendia I, Egea J, Meuth SG, Lopez MG, Kleinschnitz C, Schmidt HHHW. NOX4-dependent neuronal autotoxicity and BBB breakdown explain the superior sensitivity of the brain to ischemic damage. Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):12315-12320. doi: 10.1073/pnas.1705034114. Epub 2017 Oct 31. PMID: 29087944; PMCID: PMC5699031. 15: Geis C, Geuss E, Sommer C, Schmidt HH, Kleinschnitz C. NOX4 is an early initiator of neuropathic pain. Exp Neurol. 2017 Feb;288:94-103. doi: 10.1016/j.expneurol.2016.11.008. Epub 2016 Nov 14. PMID: 27856286. 16: Teixeira G, Szyndralewiez C, Molango S, Carnesecchi S, Heitz F, Wiesel P, Wood JM. Therapeutic potential of NADPH oxidase 1/4 inhibitors. Br J Pharmacol. 2017 Jun;174(12):1647-1669. doi: 10.1111/bph.13532. Epub 2016 Jul 14. PMID: 27273790; PMCID: PMC5446584. 17: Rousset F, Hazane-Puch F, Pinosa C, Nguyen MV, Grange L, Soldini A, Rubens- Duval B, Dupuy C, Morel F, Lardy B. IL-1beta mediates MMP secretion and IL-1beta neosynthesis via upregulation of p22(phox) and NOX4 activity in human articular chondrocytes. Osteoarthritis Cartilage. 2015 Nov;23(11):1972-80. doi: 10.1016/j.joca.2015.02.167. PMID: 26521743. 18: Hirschhäuser C, Bornbaum J, Reis A, Böhme S, Kaludercic N, Menabò R, Di Lisa F, Boengler K, Shah AM, Schulz R, Schmidt HH. NOX4 in Mitochondria: Yeast Two- Hybrid-Based Interaction with Complex I Without Relevance for Basal Reactive Oxygen Species? Antioxid Redox Signal. 2015 Nov 10;23(14):1106-12. doi: 10.1089/ars.2014.6238. Epub 2015 Aug 3. PMID: 26237157; PMCID: PMC4657509. 19: Qiu S, Mintz JD, Salet CD, Han W, Giannis A, Chen F, Yu Y, Su Y, Fulton DJ, Stepp DW. Increasing muscle mass improves vascular function in obese (db/db) mice. J Am Heart Assoc. 2014 Jun 25;3(3):e000854. doi: 10.1161/JAHA.114.000854. PMID: 24965025; PMCID: PMC4309080. 20: Schildknecht S, Weber A, Gerding HR, Pape R, Robotta M, Drescher M, Marquardt A, Daiber A, Ferger B, Leist M. The NOX1/4 inhibitor GKT136901 as selective and direct scavenger of peroxynitrite. Curr Med Chem. 2014;21(3):365-76. doi: 10.2174/09298673113209990179. PMID: 23848532.