KN-62

KN-62
Names
Preferred IUPAC name
4-[(2S)-2-(N-Methylisoquinoline-5-sulfonamido)-3-oxo-3-(4-phenylpiperazin-1-yl)propyl]phenyl isoquinoline-5-sulfonate
Identifiers
CAS Number
  • 127191-97-3 checkY
3D model (JSmol)
  • Interactive image
ChemSpider
  • 4471558
IUPHAR/BPS
  • 4235
MeSH C063302
PubChem CID
  • 5312126
UNII
  • 63HM46XPOW checkY
CompTox Dashboard (EPA)
  • DTXSID70925812 Edit this at Wikidata
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
  • 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
Chemical compound

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

  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. doi:10.1124/mol.54.1.22. 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.
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Receptor
(ligands)
P0 (adenine)
P1
(adenosine)
P2
(nucleotide)
P2X
(ATPTooltip Adenosine triphosphate)
P2Y
Transporter
(blockers)
CNTsTooltip Concentrative nucleoside transporters
ENTsTooltip Equilibrative nucleoside transporters
PMATTooltip Plasma membrane monoamine transporter
Enzyme
(inhibitors)
XOTooltip Xanthine oxidase
Others
Others
See also: Receptor/signaling modulators


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