139298-40-1 Usage
Description
KN-93 is a selective inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), competitively blocking the calmodulin (CaM) binding to the kinase with a Ki value of 370 nM. It is a cell-permeable, reversible, and competitive inhibitor that selectively binds to the CaM binding site of the enzyme, preventing the association of CaM with CaMKII. KN-93 does not significantly affect the activities of other kinases such as PKA, PKC, MLCK, or Ca2+-phosphodiesterase. It has been used in various applications due to its ability to induce G1 cell cycle arrest and apoptosis in certain cell lines.
Uses
1. Used in Neuroscience Research:
KN-93 is used as an inhibitor to block αCaMKII (Ca2+/calmodulin-dependent protein kinase IIα) for studying the role of CaMKII in synaptic plasticity, learning, and memory.
2. Used in Cardiac Myocyte Research:
KN-93 is used as a CaMKII inhibitor to pre-treat hippocampal slices to investigate the roles of CaMKII in Ca2+-induced Ca2+ release in cardiac myocytes.
3. Used in Cellular and Molecular Biology:
KN-93 is used to treat cells and alter the cytoskeleton (CSK) structure and function during experiments, providing insights into the regulation of cellular processes by CaMKII.
4. Used in Pharmacology:
KN-93 is used as a potent and selective inhibitor of Ca2+/Calmoduline-dependent protein kinase II (CaMKII) to study the effects of CaMKII inhibition on various cellular processes and signaling pathways.
5. Used in Drug Development:
KN-93 serves as a starting point for the development of new drugs targeting CaMKII, which may have potential therapeutic applications in treating various diseases and conditions related to the dysregulation of CaMKII activity.
6. Used in Chemical Synthesis:
KN-93 is a sulfonamide resulting from the formal condensation of p-methoxybenzenesulfonic acid with the anilino nitrogen of 2-(aminomethyl)-N-(2-hydroxyethyl)aniline, where the hydrogens of the primary amino group have been replaced by methyl and p-chlorocinnamyl groups. It is a white to off-white powder and can be used in the synthesis of related compounds for further research and development.
Biological Activity
Potent inhibitor of CaM kinase II (IC 50 = 0.37 μ M). Also a direct extracellular open channel blocker of voltage-gated potassium channels (IC 50 = 307 nM for Kv1.5); independent of CaM kinase II inhibition.
Biochem/physiol Actions
KN-93 is a selective Ca2+/calmodulin-dependent protein kinase II inhibitor, which has been implicated in the regulation of smooth muscle contractility. CaM kinase II activation was inhibited by KN-93 pretreatment (IC50 ~1 μM). KN-93 inhibited histamine-induced tonic force maintenance, whereas early force development and MLC20 phosphorylation responses during the entire time course were unaffected. Both force development and maintenance in response to KCl were inhibited by KN-93. Rapid increases in KCl-induced MLC20 phosphorylation were also inhibited by KN-93, whereas steady-state MLC20 phosphorylation responses were unaffected. In contrast, phorbol 12,13-dibutyrate (PDBu) did not activate CaM kinase II and PDBu-stimulated force development was unaffected by KN-93. Thus KN-93 appears to target a step(s) essential for force maintenance in response to physiological stimuli, suggesting a role for CaM kinase II in regulating tonic contractile responses in arterial smooth muscle. Pharmacological activation of protein kinase C bypasses the KN-93 sensitive step.
Check Digit Verification of cas no
The CAS Registry Mumber 139298-40-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,9,2,9 and 8 respectively; the second part has 2 digits, 4 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 139298-40:
(8*1)+(7*3)+(6*9)+(5*2)+(4*9)+(3*8)+(2*4)+(1*0)=161
161 % 10 = 1
So 139298-40-1 is a valid CAS Registry Number.
InChI:InChI=1/C26H29ClN2O4S/c1-28(17-5-6-21-9-11-23(27)12-10-21)20-22-7-3-4-8-26(22)29(18-19-30)34(31,32)25-15-13-24(33-2)14-16-25/h3-16,30H,17-20H2,1-2H3/b6-5+
