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Chemical Structure| 139298-40-1 Chemical Structure| 139298-40-1

Structure of KN-93
CAS No.: 139298-40-1

Chemical Structure| 139298-40-1

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KN-93 is a potent Ca2+/calmodulin-dependent protein kinase II (CaMKII) selective inhibitor with Ki of 370 nM.

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Product Details of KN-93

CAS No. :139298-40-1
Formula : C26H29ClN2O4S
M.W : 501.04
SMILES Code : O=S(C1=CC=C(OC)C=C1)(N(C2=CC=CC=C2CN(CC=CC3=CC=C(Cl)C=C3)C)CCO)=O
MDL No. :MFCD00236424
InChI Key :LLLQTDSSHZREGW-AATRIKPKSA-N
Pubchem ID :5312122

Safety of KN-93

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H332
Precautionary Statements:P280

Isoform Comparison

Biological Activity

Target
  • CaMKII

    CaMKII, Ki:0.37 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
Mouse astrocytes 10 µM 15 min Inhibition of CaMKII activity, reducing MLC1 protein dimerization Cells. 2022 Aug 26;11(17):2656.
HEK293T cells 10 μM 4 h To screen the upstream kinase for PRMT6 Mol Cell. 2021 Mar 18;81(6):1276-1291.e9.
U251 cells 10 µM 15 min Inhibition of CaMKII activity, reducing MLC1 protein phosphorylation Cells. 2022 Aug 26;11(17):2656.
BAP1-KO MeT-5A cells 7.5 µM 48 h KN-93 significantly induced apoptosis in BAP1-KO cells by increasing intracellular Ca2+ concentration and inhibiting CAMK2D activity. Cell Death Discov. 2023 Jul 21;9(1):257.
BAP1-KO HOMC-D4 cells 7.5 µM 48 h KN-93 significantly induced apoptosis in BAP1-KO cells by increasing intracellular Ca2+ concentration and inhibiting CAMK2D activity. Cell Death Discov. 2023 Jul 21;9(1):257.
Y-MESO-9 cells 7.5 µM 48 h KN-93 significantly induced apoptosis in BAP1-KO cells by increasing intracellular Ca2+ concentration and inhibiting CAMK2D activity. Cell Death Discov. 2023 Jul 21;9(1):257.
Human AC-16 cardiomyocytes 50 μM 1 h Pre-treatment with KN-93 reduced doxorubicin-induced ROS generation and cell death in RGS11 knockout AC-16 cells. Redox Biol. 2022 Nov;57:102487.
HEK293 cells 10 μM 14 h To investigate the inhibitory effect of KN-93 on CaMKII, it was found that KN-93 aggravated the accumulation of ubiquitinated proteins. EMBO Rep. 2024 Oct;25(10):4488-4514.
HeLa cells 10 μM 14 h To investigate the inhibitory effect of KN-93 on CaMKII, it was found that KN-93 aggravated the accumulation of ubiquitinated proteins. EMBO Rep. 2024 Oct;25(10):4488-4514.
NRVM (neonatal rat ventricular myocytes) 10 μM 24 h KN-93 treatment significantly reduced the p-CaMKII levels in PRMT1-depleted cells, restored cell size, and attenuated the increase in ANP and β-MHC gene expression. Nat Commun. 2018 Nov 30;9(1):5107.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice LPS-induced acute lung injury model Intraperitoneal injection 10mg/kg The first injection was performed 2h before LPS administration, followed by injections every 24h for 48h. KN-93 suppressed the phosphorylation of CaMK4 and significantly inhibited NLRP3 inflammasome activation, leading to reduced IL-1β and IL-18 production, and ameliorated LPS-induced acute lung injury. Front Immunol. 2022 Jun 6;13:890710
SCID mice BAP1-KO Y-MESO-9 xenograft model Intraperitoneal injection 15 mg/kg Administered on days 0, 4, 8,13, and 16, lasting 16 days KN-93 significantly suppressed tumor growth of BAP1-KO Y-MESO-9 cells without causing weight loss and inhibited tumor growth by promoting apoptosis. Cell Death Discov. 2023 Jul 21;9(1):257.
Mice Diabetic myocardial ischemia model Direct injection into the left ventricle 300 μg/kg Single dose 10 minutes before surgery KN-93 significantly increased the concentration levels of circulating myocardial enzymes and infarct size in DM hearts, decreased the release of CGRP, attenuated the recovery of cardiac function, and increased the interstitial fibrosis area, indicating that CaMKII plays an important role in PF-mediated cardioprotection. Cell Biosci. 2016 Jun 1;6:37
Mice Isoflurane anesthesia model Intracerebroventricular injection 1 mM Single injection, lasting 7 days KN93 significantly diminished the protective effect of GLYX-13 on cognitive function and NR2B, CaMKII, and CREB levels, indicating that GLYX-13 ameliorates isoflurane-induced cognitive dysfunction via the NR2B/CaMKII/CREB signaling pathway. Neural Regen Res. 2020 Jan;15(1):128-135
Mice Chronic doxorubicin-induced cardiotoxicity model Intraperitoneal injection 8 mg/kg Every 4 days, total of 2 doses KN-93 treatment significantly alleviated cardiac fibrosis in RGS11 knockdown mice. Redox Biol. 2022 Nov;57:102487.
Nude mice MDA-MB-231 xenograft model Intraperitoneal injection 10 mg/kg Once every three days for 12 days To investigate the anti-tumor efficacy of KN-93 in combination with proteasome inhibitors, it was found that the combination significantly enhanced anti-tumor activity. EMBO Rep. 2024 Oct;25(10):4488-4514.
Mice Cardiac-specific PRMT1 knockout mice Intraperitoneal injection 10 μM/kg Once daily for 8 days KN-93 treatment improved cardiac function in PRMT1-deficient mice, reduced left ventricular dilation and fibrosis, and decreased the expression of ANP and BNP. Nat Commun. 2018 Nov 30;9(1):5107.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.00mL

0.40mL

0.20mL

9.98mL

2.00mL

1.00mL

19.96mL

3.99mL

2.00mL

References

[1]Sumi M, Kiuchi K, et al. The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. Biochem Biophys Res Commun. 1991 Dec 31;181(3):968-75.

[2]Rezazadeh S, Claydon TW, et al. KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a calcium/calmodulin-dependent protein kinase II inhibitor, is a direct extracellular blocker of voltage-gated potassium channels. J Pharmacol Exp Ther. 2006 Apr;317(1):292-9. Epub 2005 Dec 20.

[3]Hegyi B, Chen-Izu Y, et al. KN-93 inhibits IKr in mammalian cardiomyocytes. J Mol Cell Cardiol. 2015 Dec;89(Pt B):173-6.

[4]Sumi M, Kiuchi K, Ishikawa T, Ishii A, Hagiwara M, Nagatsu T, Hidaka H. The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12h cells. Biochem Biophys Res Commun. 1991 Dec 31;181(3):968-75. doi: 10.1016/0006-291x(91)92031-e. PMID: 1662507.

[5]Rezazadeh S, Claydon TW, Fedida D. KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a calcium/calmodulin-dependent protein kinase II inhibitor, is a direct extracellular blocker of voltage-gated potassium channels. J Pharmacol Exp Ther. 2006 Apr;317(1):292-9. doi: 10.1124/jpet.105.097618. Epub 2005 Dec 20. PMID: 16368898.

[6]Hegyi B, Chen-Izu Y, Jian Z, Shimkunas R, Izu LT, Banyasz T. KN-93 inhibits IKr in mammalian cardiomyocytes. J Mol Cell Cardiol. 2015 Dec;89(Pt B):173-6. doi: 10.1016/j.yjmcc.2015.10.012. Epub 2015 Oct 14. PMID: 26463508; PMCID: PMC4689637.

 

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