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Purity: ≥98%
GKT136901 is a novel and potent NOX1/4 inhibitor acting by blocking tumor angiogenesis through a PPARα mediated mechanism and selective scavenging of peroxynitrite (PON).
| ln Vitro |
In high MPT cells, GKT136901 (10 μM; 30 minutes) significantly disconnects O2 induced by D-short circuit. GKT136901 (10 μM; 30 minutes) neutralizes the impact of elevated D- on MPT cell p38MAP activation [4]. Amphetamine production is eliminated and H2O 2 is increased in HBMEC by GKT136901 (10 μM; 2 hours) [4]. HBMEC shells are shielded from METH-induced blood-brain barrier (BBB) dysfunction by GKT136901 (10 μM; 2 hours) [5].
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| ln Vivo |
In type 2 diabetic mice, GKT136901 (30-90 mg/kg; daily injection for 16 weeks) exhibits renoprotective properties [6].
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| Animal Protocol |
Animal/Disease Models: Male db/db and db/m mice (8 weeks) [6] ]
Doses: 30, 90 mg/kg Route of Administration: Oral daily for 16 weeks Experimental Results: Albuminuria, sulfur in diabetic mice Phosphorylation of barbituric acid reactive substances (TBARS) and renal ERK1/2 is diminished, and renal structure is preserved. There is no effect on blood sugar, BP (blood pressure) and body weight. |
| References |
[1]. Laleu B, et, al. First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J Med Chem. 2010 Nov 11;53(21):7715-30.
[2]. Teixeira G, et, al. Therapeutic potential of NADPH oxidase 1/4 inhibitors. Br J Pharmacol. 2017 Jun;174(12):1647-1669. [3]. Schildknecht S, et, al. The NOX1/4 inhibitor GKT136901 as selective and direct scavenger of peroxynitrite. Curr Med Chem. 2014;21(3):365-76. [4]. Sedeek M, et, al. Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am J Physiol Renal Physiol. 2010 Dec;299(6):F1348-58. [5]. Hwang JS, et, al. GKT136901 protects primary human brain microvascular endothelial cells against methamphetamine-induced blood-brain barrier dysfunction. Life Sci. 2020 Sep 1;256:117917. [6]. Sedeek M, et, al. 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. |
| Molecular Formula |
C19H15CLN4O2
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|---|---|
| Molecular Weight |
366.8
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| Exact Mass |
366.0884
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| CAS # |
955272-06-7
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| Related CAS # |
GKT136901 hydrochloride;1254507-01-1
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| SMILES |
O=C1N(C2=CC=CC=C2Cl)NC(C1=C(C)N3CC4=NC=CC=C4)=CC3=O
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| InChi Key |
DNKYHHFCPXKFIY-UHFFFAOYSA-N
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| 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
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| Chemical Name |
2-(2-Chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-dione
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| Synonyms |
GKT136901 GKT-136901 GKT 136901
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~90.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7263 mL | 13.6314 mL | 27.2628 mL | |
| 5 mM | 0.5453 mL | 2.7263 mL | 5.4526 mL | |
| 10 mM | 0.2726 mL | 1.3631 mL | 2.7263 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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