KN-62 is a derivative of isoquinolinesulfonamide, it is a selective, specific and cell permeable inhibitor of Ca2+/calmodulin-dependent kinase type II (CaMK II) with IC₅₀ of 900nM, charactered by

hydrophobicity In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

. KN-62 also potently inhibits the purinergic receptor P2X7.

Inhibitory mechanism on CaMK II

KN-62 blocks the combination of CaM and CaMK II by binding directly to the

calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bin ...

binding site of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

, disenables CaMK II's

autophosphorylation Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself. In eukaryotes, this process occurs by the addition of a phosphate group to serine, threonine o ...

, consequently leading inactivation. Kinetic analysis exhibits that this inhibitory effect of KN-62 is competitive with respect to calmodulin. Since KN-62 binds to the calmodulin binding site of CaMK II, KN-62 doesn't inhibit activity of autophosphorylated CaMK II.
Besides, KN-62 also acts as a potent non-competitive

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...

at the purinergic receptor

P2RX7 P2X purinoceptor 7 is a protein that in humans is encoded by the ''P2RX7'' gene. The product of this gene belongs to the family of purinoceptors for ATP. Multiple alternatively spliced variants which would encode different isoforms have been id ...

with

IC50 The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance ...

of 15nM.

References

Protein biosynthesis Receptor antagonists Sulfonamides {{organic-compound-stub