KN-62
Based on 12 publication(s) in Google Scholar
KN-62 is a selective and reversible inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with a Ki of 0.9 μM for rat brain CaMK-II. KN-62 directly binds to the calmodulin binding site of CaMK-II. KN-62 displays noncompetitive antagonism at P2X7 receptors in HEK293 cells, with an IC50 value of approximately 15 nM.
For research use only. We do not sell to patients.
- Purity: 99.00%
- CAS No.: 127191-97-3
- Formula: C38H35N5O6S2
- Molecular Weight:721.84
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) KN-62
More- Cell Commun Signal. 2021 Oct 11;19(1):103. [Abstract]
- Cell Syst. 2018 Apr 25;6(4):424-443.e7. [Abstract]
- PLoS Biol. 2024 Mar 25;22(3):e3002565. [Abstract]
- Clin Transl Med. 2022 May;12(5):e849. [Abstract]
- J Mol Cell Biol. 2025 Dec 5:mjaf050. [Abstract]
- J Mol Cell Biol. 2025 Jul 28;17(2):mjaf002. [Abstract]
- Cell Biol Toxicol. 2023 Jun;39(3):679-702. [Abstract]
- Chem Biol Interact. 2025 May 28:111577. [Abstract]
- Mol Neurobiol. 2023 May;60(5):2749-2766. [Abstract]
- Acta Biochim Biophys Sin (Shanghai). 2019 Aug 5;51(8):767-777. [Abstract]
- Mol Pharmacol. 2019 Mar;95(3):294-302. [Abstract]
- PeerJ. 2022 Oct 25:10:e14192. [Abstract]
All P2X Receptor Isoforms
More
Biological Activity
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P2X7 Receptor |
CaMK II 0.9 μM (Ki) |
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Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
0.11 μM
Compound: KN-62
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Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced fluorescent ethidium accumulation at 10 uM
Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced fluorescent ethidium accumulation at 10 uM
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[PMID: 19800793] |
| HEK293 | IC50 |
0.158 μM
Compound: 1, KN62
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Antagonist activity at recombinant human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced intracellular ethidium bromide uptake after 2 hrs by fluorescence assay
Antagonist activity at recombinant human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced intracellular ethidium bromide uptake after 2 hrs by fluorescence assay
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[PMID: 25597334] |
| HEK293 | IC50 |
0.25 μM
Compound: 1; KN62
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Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium ion uptake after 2 hrs
Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium ion uptake after 2 hrs
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[PMID: 26547056] |
| HEK293 | IC50 |
0.34 μM
Compound: 1, KN-62
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Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced fluorescent ethidium accumulation
Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced fluorescent ethidium accumulation
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[PMID: 19110420] |
| HEK293 | IC50 |
158 nM
Compound: KN-62
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Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced accumulation of ethidium+ after 120 mins by fluorescence assay
Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced accumulation of ethidium+ after 120 mins by fluorescence assay
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[PMID: 24246730] |
| HEK293 | IC50 |
175 nM
Compound: 1, KN-62
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Antagonist activity at human purinergic P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium bromide uptake
Antagonist activity at human purinergic P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium bromide uptake
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[PMID: 18078749] |
| HEK293 | IC50 |
280 nM
Compound: 1
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Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium bromide uptake after 2 hrs by fluorescence analysis
Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium bromide uptake after 2 hrs by fluorescence analysis
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[PMID: 22400713] |
| HEK293 | IC50 |
96 μM
Compound: KN-62
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Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium bromide uptake after 2 hrs by fluorescence assay
Antagonist activity at human P2X7 receptor expressed in HEK293 cells assessed as inhibition of BzATP-induced ethidium bromide uptake after 2 hrs by fluorescence assay
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[PMID: 28126517] |
| THP-1 | IC50 |
0.129 μM
Compound: 1; KN62
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Antagonist activity at P2X7 receptor expressed in LPS/IFNgamma-differentiated human THP1 cells assessed as inhibition of BzATP-induced IL-1beta production after 4 hrs by ELISA
Antagonist activity at P2X7 receptor expressed in LPS/IFNgamma-differentiated human THP1 cells assessed as inhibition of BzATP-induced IL-1beta production after 4 hrs by ELISA
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[PMID: 26547056] |
| THP-1 | IC50 |
0.143 μM
Compound: 1, KN62
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Antagonist activity at P2X7 receptor in LPS/IFN-gamma-differentiated human THP1 cells assessed as inhibition of BzATP-induced IL-1beta release preincubated for 30 mins followed by BzATP induction measured after 30 mins by ELISA
Antagonist activity at P2X7 receptor in LPS/IFN-gamma-differentiated human THP1 cells assessed as inhibition of BzATP-induced IL-1beta release preincubated for 30 mins followed by BzATP induction measured after 30 mins by ELISA
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[PMID: 25597334] |
| THP-1 | IC50 |
0.3 μM
Compound: KN-62
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Antagonist activity at P2X7 receptor in human THP1 cells assessed as inhibition of BzATP-induced pore formation
Antagonist activity at P2X7 receptor in human THP1 cells assessed as inhibition of BzATP-induced pore formation
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[PMID: 19540765] |
| THP-1 | IC50 |
120 nM
Compound: 1
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Antagonist activity at human P2X7 receptor in human THP1 cells assessed as inhibition of BzATP-induced IL8 release pretreated for 30 mins before bzATP challenge measured after 30 mins by ELISA
Antagonist activity at human P2X7 receptor in human THP1 cells assessed as inhibition of BzATP-induced IL8 release pretreated for 30 mins before bzATP challenge measured after 30 mins by ELISA
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[PMID: 22400713] |
| THP-1 | IC50 |
188 nM
Compound: 1, KN-62
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Inhibition of BzATP-stimulated IL1-beta release in human THP1 cells by ELISA
Inhibition of BzATP-stimulated IL1-beta release in human THP1 cells by ELISA
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[PMID: 18078749] |
| THP-1 | IC50 |
81 nM
Compound: 1, KN-62
|
Inhibition of Bz-ATP-induced IL1-beta release in LPS/IFN-gamma-differentiated human THP1 cells by ELISA
Inhibition of Bz-ATP-induced IL1-beta release in LPS/IFN-gamma-differentiated human THP1 cells by ELISA
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[PMID: 19110420] |
KN-62 potently antagonizes ATP-stimulated Ba2+ influx into fura-2 loaded human lymphocytes with an IC50 of 12.7 nM and complete inhibition of the flux at a concentration of 500 nM[1].
KN-62 does not inhibit the activity of autophosphorylated Ca2+/CaM kinase II. KN-62 inhibits the Ca2+/calmodulin-dependent autophosphorylation of both alpha (50 kDa) and beta (60 kDa) subunits of Ca2+/CaM kinase II dose dependently in the presence or absence of exogenous substrate[2].
In human leukemic B lymphocytes, KN-62 reduces the rate of permeability increase to larger permeant cations, like ethidium, induced by Bz-ATP with an IC50 of 13.1 nM[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
KN-62 (1 μg/site, i.c.v.) prevents the antidepressant-like behavior and antidepressant-like behaviors of ZnCl2 (10 mg/kg, p.o.)[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 127191-97-3
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Appearance Solid
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Molecular Weight 721.84
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Formula C38H35N5O6S2
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Color Off-white to yellow
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SMILES
O=C(N1CCN(C2=CC=CC=C2)CC1)[C@H](CC3=CC=C(C=C3)OS(=O)(C4=CC=CC5=C4C=CN=C5)=O)N(C)S(=O)(C6=CC=CC7=C6C=CN=C7)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 1 year -20°C 6 months
Publications (12)
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Journal Impact Factor
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Most Recent
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Cell Commun Signal
Zinc-mediated activation of CREB pathway in proliferation of pulmonary artery smooth muscle cells in pulmonary hypertension. [Abstract]2021 Oct 11;19(1):103. PMID: 34635097 -
Cell Syst
A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations. [Abstract]2018 Apr 25;6(4):424-443.e7. PMID: 29655704 -
PLoS Biol
The scale of zebrafish pectoral fin buds is determined by intercellular K+ levels and consequent Ca2+-mediated signaling via retinoic acid regulation of Rcan2 and Kcnk5b. [Abstract]2024 Mar 25;22(3):e3002565. PMID: 38527087 -
Clin Transl Med
Hepatic pannexin-1 mediates ST2+ regulatory T cells promoting resolution of inflammation in lipopolysaccharide-induced endotoxemia. [Abstract]2022 May;12(5):e849. PMID: 35593197 -
J Mol Cell Biol
Canonical Wnt signaling affects calcium homeostasis in serum-treated AC16 cells through MLN-mediated SERCA2a regulation. [Abstract]2025 Dec 5:mjaf050. PMID: 41348974 -
J Mol Cell Biol
Wnt/β-catenin pathway induces cardiac dysfunction via AKAP6-mediated RyR2 phosphorylation and sarcoplasmic reticulum calcium leakage. [Abstract]2025 Jul 28;17(2):mjaf002. PMID: 40097291 -
Cell Biol Toxicol
CaMKII and CaV3.2 T-type calcium channel mediate Connexin-43-dependent inflammation by activating astrocytes in vincristine-induced neuropathic pain. [Abstract]2023 Jun;39(3):679-702. PMID: 34286406 -
Chem Biol Interact
Platycodin D reverses tumor necrosis factor-α-induced endothelial dysfunction by increasing nitric oxide through G protein-coupled estrogen receptor-mediated eNOS activity. [Abstract]2025 May 28:111577. PMID: 40447174 -
Mol Neurobiol
Transmission of NLRP3-IL-1β Signals in Cerebral Ischemia and Reperfusion Injury: from Microglia to Adjacent Neuron and Endothelial Cells via IL-1β/IL-1R1/TRAF6. [Abstract]2023 May;60(5):2749-2766. PMID: 36717480 -
Acta Biochim Biophys Sin (Shanghai)
Combined bone marrow stromal cells and oxiracetam treatments ameliorates acute cerebral ischemia/reperfusion injury through TRPC6. [Abstract]2019 Aug 5;51(8):767-777. PMID: 31236585 -
Mol Pharmacol
Inhibition of Interleukin 10 Transcription through the SMAD2/3 Signaling Pathway by Ca2+-Activated K+ Channel KCa3.1 Activation in Human T-Cell Lymphoma HuT-78 Cells. [Abstract]2019 Mar;95(3):294-302. PMID: 30622214 -
PeerJ
Icariside II induces rapid phosphorylation of endothelial nitric oxide synthase via multiple signaling pathways. [Abstract]2022 Oct 25:10:e14192. PMID: 36312762
Solvent & Solubility
DMSO : ≥ 100 mg/mL (138.53 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.46 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Lymphocytes (1×107/mL) are cultured with [3H]-oleic acid (2-5 μCi/mL, specific activity 10 Ci/mmol) for 20-24 h in RPMI-1640 medium supplemented with Gentamicin (40 μg/mL), 10% heat inactivated foetal calf serum (FCS) at 37°C to label membrane phospholipids. Labelled cells are washed twice in HEPES buffered saline followed by a final wash in either HEPES buffered saline or 150 mM KCl medium containing HEPES 10 mM, pH 7.4, bovine serum albumin (BSA) 1 g/L and D-glucose 5 mM and CaCl2 1 mM. Three mL aliquots containing 1.1×10< sup>7/mL lymphocytes are warmed to 37°C and incubated with or without KN-62 or KN-04 (1 nM-500 nM) for 5 min, then 900 mL aliquots are added to 100 uL butanol (final concentration 30 mM) for a further 5 min, and stimulated with 1 mM ATP for 15 min with gentle mixing in the continued presence of inhibitor or diluent. The phospholipase D reaction is terminated by addition of 1 mL of 20 mM MgCl2 followed by centrifugation and addition of 1 mL ice cold methanol. Membrane lipids are extracted into chloroform/HCl at 4°C under N2, and separated by silica gel thin layer chromatography (t.l.c.) with the solvent system, ethyl acetate/iso-octane/acetic acid/water (13:2:3:10, v/v) under saturating conditions. Sample spots are located by autoradiography and [3H]-phosphatidylbutanol ([3H]-PBut) spots identified by an authentic standard. [3H]-PBut and [3H]-phospholipid spots are scraped into scintillant fluid (PPO in toluene, 4 g/L) and counted in a liquid scintillation counter. The quantity of [3H]-PBut is presented as a percentage of total 3H labelled-cellular phospholipids. Phospholipase D assays are performed in triplicate[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
All experiments are performed using adherent HEK293 cells stably transfected with cDNA encoding the human P2X7 receptor. Adherent cells on 12-well polylysine-coated plates are incubated at 37°C in 1 mL physiological salt solution (125 mM NaCl, 5 mM KCl, 1 mM MgCl2, 1.5 mM CaCl2, 25 mM NaHEPES (pH 7.5), 10 mM D-glucose, 1 mg/mL BSA). Antagonists(e.g., KN-62) are added from 1,000× stock solutions dissolved in DMSO. Cells are preincubated with antagonists (e.g., KN-62) for 15 min prior to stimulation for 10 min with 3 mM ATP (final concentration). Reactions are terminated by rapid aspiration of the extracellular medium in each well. The adherent cells in each well are then extracted overnight with 1 mL 10% HNO3. K+ content in these nitric acid extracts is assayed by atomic absorbance spectrophotometry. Duplicate or triplicate wells are run for all test conditions in each separate experiment[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[3]
Female Swiss mice (45-55 days old, weighing 30-45 g) are used. The following drugs are used: ZnCl2 (1 or 10 mg/kg), H-89 (1 μg/site, PKA inhibitor), KN-62 (1 μg/site, CAMKII inhibitor), chelerythrine (1 μg/site, PKC inhibitor), PD98059 (5 μg/site, MAPKK/MEK 1/2 inhibitor), U0126 (5 μg/site, MEK1/2 inhibitor), LY294002 (10 nmol/site, PI3K inhibitor), AR-A014418 (0.001 μg/site, selective GSK-3β inhibitor). ZnCl2 is dissolved in distilled water and administered orally (p.o.). H-89, KN-62, chelerythrine, PD98059, U0126, LY294002, AR-A014418 are dissolved in saline (0.9% NaCl) at a final concentration of 1% dimethyl sulfoxide (DMSO) and administered by intracerebroventricular (i.c.v.) route. The drugs are freshly prepared before treatment and administered in a volume of 10 mL/kg body weight (p.o. route) or 5 μL/site (i.c.v. route). Control animals receive the appropriate vehicle.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (287 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Gargett CE, et al. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes. Br J Pharmacol. 1997 Apr;120(8):1483-90. [Content Brief]
[2]. H Hidaka, et al. Pharmacology of protein kinase inhibitors. Annu Rev Pharmacol Toxicol. 1992;32:377-97. [Content Brief]
[3]. Miso Park, et al. Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer: effects on small extracellular vesicles production. Sci Rep. 2019 Aug 12;9(1):11587. [Content Brief]
[4]. Ravi RG, et al. Potent P2X7 Receptor Antagonists: Tyrosyl Derivatives Synthesized Using a Sequential Parallel Synthetic Approach. Drug Dev Res. 2001 Oct;54(2):75-87. [Content Brief]
[5]. Manosso LM, et al. Antidepressant-like effect of zinc is dependent on signaling pathways implicated in BDNF modulation. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:59-67. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.3853 mL | 6.9267 mL | 13.8535 mL | 34.6337 mL |
| 5 mM | 0.2771 mL | 1.3853 mL | 2.7707 mL | 6.9267 mL | |
| 10 mM | 0.1385 mL | 0.6927 mL | 1.3853 mL | 3.4634 mL | |
| 15 mM | 0.0924 mL | 0.4618 mL | 0.9236 mL | 2.3089 mL | |
| 20 mM | 0.0693 mL | 0.3463 mL | 0.6927 mL | 1.7317 mL | |
| 25 mM | 0.0554 mL | 0.2771 mL | 0.5541 mL | 1.3853 mL | |
| 30 mM | 0.0462 mL | 0.2309 mL | 0.4618 mL | 1.1545 mL | |
| 40 mM | 0.0346 mL | 0.1732 mL | 0.3463 mL | 0.8658 mL | |
| 50 mM | 0.0277 mL | 0.1385 mL | 0.2771 mL | 0.6927 mL | |
| 60 mM | 0.0231 mL | 0.1154 mL | 0.2309 mL | 0.5772 mL | |
| 80 mM | 0.0173 mL | 0.0866 mL | 0.1732 mL | 0.4329 mL | |
| 100 mM | 0.0139 mL | 0.0693 mL | 0.1385 mL | 0.3463 mL |
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