KN-62

KN-62
Names
	IUPAC name 4-[(2S)-2-[(5-isoquinolinylsulfonyl)methylamino]-3-oxo-3-(4-phenyl-1-piperazinyl)propyl] phenyl isoquinolinesulfonic acid ester
Identifiers
CAS Number	127191-97-3 ;
3D model (JSmol)	Interactive image;
ChemSpider	4471558;
IUPHAR/BPS	4235;
MeSH	C063302
PubChem CID	5312126;
UNII	63HM46XPOW ;
CompTox Dashboard (EPA)	DTXSID70925812 ;
	InChI InChI=1S/C38H35N5O6S2/c1-41(50(45,46)36-11-5-7-29-26-39-19-17-33(29)36)35(38(44)43-23-21-42(22-24-43)31-9-3-2-4-10-31)25-28-13-15-32(16-14-28)49-51(47,48)37-12-6-8-30-27-40-20-18-34(30)37/h2-20,26-27,35H,21-25H2,1H3/t35-/m0/s1 Key: RJVLFQBBRSMWHX-DHUJRADRSA-N; InChI=1/C38H35N5O6S2/c1-41(50(45,46)36-11-5-7-29-26-39-19-17-33(29)36)35(38(44)43-23-21-42(22-24-43)31-9-3-2-4-10-31)25-28-13-15-32(16-14-28)49-51(47,48)37-12-6-8-30-27-40-20-18-34(30)37/h2-20,26-27,35H,21-25H2,1H3/t35-/m0/s1 Key: RJVLFQBBRSMWHX-DHUJRADRBK;
	SMILES CN([C@@H](CC1=CC=C(C=C1)OS(=O)(=O)C2=CC=CC3=C2C=CN=C3)C(=O)N4CCN(CC4)C5=CC=CC=C5)S(=O)(=O)C6=CC=CC7=C6C=CN=C7;
Properties
Chemical formula	C38H35N5O6S2
Molar mass	721.84 g/mol
Boiling point	964.7±75.0 °C at 760 mmHg
Hazards
Flash point	537.3±37.1 °C
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	Infobox references

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,[1] charactered by hydrophobicity. KN-62 also potently inhibits the purinergic receptor P2X7.[2]

Inhibitory mechanism on CaMK II

KN-62 blocks the combination of CaM and CaMK II by binding directly to the calmodulin binding site of the enzyme, disenables CaMK II's autophosphorylation, consequently leading inactivation. Kinetic analysis exhibits that this inhibitory effect of KN-62 is competitive with respect to calmodulin.[3] 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 at the purinergic receptor P2RX7 with IC50 of 15nM.

References

"avtivity in vitro and in vivo of KN-62". selleck chemicals.
Humphreys, BD; Virginio, C; Surprenant, A; Rice, J; Dubyak, GR (July 1998). "Isoquinolines as antagonists of the P2X7 nucleotide receptor: high selectivity for the human versus rat receptor homologues". Molecular Pharmacology. 54 (1): 22–32. PMID 9658186.
Okazaki K, et al. (Sep 1994). "KN-62, a specific Ca++/calmodulin-dependent protein kinase inhibitor, reversibly depresses the rate of beating of cultured fetal mouse cardiac myocytes". J Pharmacol Exp Ther. 270 (3): 1319–24. PMID 7932185.

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[1] "avtivity in vitro and in vivo of KN-62". selleck chemicals.

[2] Humphreys, BD; Virginio, C; Surprenant, A; Rice, J; Dubyak, GR (July 1998). "Isoquinolines as antagonists of the P2X7 nucleotide receptor: high selectivity for the human versus rat receptor homologues". Molecular Pharmacology. 54 (1): 22–32. PMID 9658186.

[3] Okazaki K, et al. (Sep 1994). "KN-62, a specific Ca++/calmodulin-dependent protein kinase inhibitor, reversibly depresses the rate of beating of cultured fetal mouse cardiac myocytes". J Pharmacol Exp Ther. 270 (3): 1319–24. PMID 7932185.