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Chemical Structure| 127191-97-3 Chemical Structure| 127191-97-3

Structure of KN-62
CAS No.: 127191-97-3

Chemical Structure| 127191-97-3

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KN-62 is a selective and potent inhibitor of calmodulin-dependent protein kinase II (CaMK-II) with IC50 of 0.9 μM, KN-62 also displays noncompetitive antagonism at P2X7 receptors in HEK293 cells, with an IC50 value of approximately 15 nM..

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Product Details of KN-62

CAS No. :127191-97-3
Formula : C38H35N5O6S2
M.W : 721.84
SMILES Code : 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
MDL No. :MFCD00083180
InChI Key :RJVLFQBBRSMWHX-DHUJRADRSA-N
Pubchem ID :5312126

Safety of KN-62

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H317-H319
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • CaMKII

    CaMKII, Ki:0.9 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
HP cells (HEK-293 cells stably transfected with rat PROT cDNA) 25 μM 1 hour KN-62 (CaMK II inhibitor) stimulates PRO uptake and abolishes thapsigargin inhibition, indicating PROT regulation by CaMK II. PMC1571857
HP cells (HEK-293 cells stably transfected with rat PROT cDNA) 25 μM 1 hour KN-62 (a CaMK II inhibitor) stimulates PRO uptake and abolishes the thapsigargin inhibitory effect, indicating that PROT is regulated by CaMK II. PMC1571857
Human B-lymphocytes 1 μM 5 min Inhibited ATP-induced 86Rb+ efflux by 96.0% PMC1575114
PBMCs 1 µM 24 hours To evaluate the effect of KN-62 on BzATP-inhibited IL-21 production by cTfh cells. KN-62 partially rescued the IL-21 production by cTfh cells. PMC11263008
PBMCs 1 µM 24 hours To evaluate the effect of KN-62 on BzATP-induced apoptosis of cTfh cells. KN-62 mitigated the apoptosis of cTfh cells induced by BzATP. PMC11263008
PBMCs 1 µM 3 days To evaluate the effect of KN-62 on BzATP-inhibited proliferation of cTfh cells. KN-62 partially rescued the proliferative response of cTfh cells. PMC11263008
GT1-7 cells 10 μM 30 min KN-62 prevented the histamine-induced desensitization of calcium signals in GT1-7 cells, indicating a crucial role for calcium/calmodulin-dependent protein kinase II (CaMKII) in histamine H1 receptor desensitization. PMC1909593
Adult skeletal muscle fibers 5 μM 30 minutes KN-62 completely blocked the translocation of HDAC4-GFP from the nucleus to the cytoplasm induced by 10 Hz electrical stimulation PMC2171787
HEK293 cells 86 nM (IC50) 4 min KN-62 potently inhibited rmP2X7 receptor-mediated currents with an IC50 of 86 nM, and the inhibition was largely irreversible PMC3188921
Rat atria 10 μM 45 minutes To investigate the effect of KN-62 on stimulation-induced noradrenaline synthesis, results showed that KN-62 did not affect S-I [3H]-noradrenaline synthesis. PMC1915779
HeLa-mPanx1 cells 10 µM 5 minutes To evaluate the effect of CaMKII inhibition on Poly(I:C)-induced Panx1 HC activity. KN-62 preincubation completely prevented the Poly(I:C)-induced increase in DAPI uptake. PMC11840745
Human lymphocytes 31.5 nM (IC50) 5 minutes Inhibition of ATP-stimulated L-selectin shedding PMC1564633
Human lymphocytes 5.9 nM (IC50) 5 minutes Inhibition of ATP-stimulated phospholipase D activity PMC1564633
Human lymphocytes 13.1 nM (IC50) 5 minutes Inhibition of ATP-stimulated ethidium+ uptake PMC1564633
Human lymphocytes 12.7 nM (IC50) 5 minutes Inhibition of ATP-stimulated Ba2+ influx PMC1564633
RAW264.7 cells 10 µM 6 hours To evaluate the effect of CaMKII inhibition on Poly(I:C)-induced inflammatory response. KN-62 preincubation prevented the upregulation of IL-1β and TNF-α mRNA levels induced by Poly(I:C). PMC11840745
Rat ventricular myocytes 10 μM To investigate the inhibitory effect of KN-62 on IKATP augmented by hypoxia and GSSG. The results showed that KN-62 inhibited the IKATP augmented by hypoxia and GSSG, suggesting that the effects of both GSSG and hypoxia on KATP channels involve the activation of the CaMK II pathway. PMC4007324
HEK-293 cells up to 3 μM To test the inhibitory effect of KN-62 on mouse, human, and rat P2X4 receptors, showing no concentration-dependent inhibition at any of the receptors PMC1571843

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Rat Isolated rat heart ischemia/reperfusion injury model Perfusion 3 μM 1 min before and 3 min throughout the Ca2+-free solution perfusion, as well as 3 min after restoring normal KH solution KN-62 alleviated heart injury and calpain activity, and attenuated the binding of CAPN1 to phospho-CaMKII PMC7242471

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.39mL

0.28mL

0.14mL

6.93mL

1.39mL

0.69mL

13.85mL

2.77mL

1.39mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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