Conjugates of 5-isoquinolinesulfonylamides and oligo-D-arginine possess high affinity and selectivity towards Rho kinase (ROCK)

Bioorg Med Chem Lett. 2012 May 15;22(10):3425-30. doi: 10.1016/j.bmcl.2012.03.101. Epub 2012 Apr 4.


In the present work, conjugates of 5-isoquinolinesulfonylamides and D-arginine-rich peptides were developed into highly potent inhibitors for basophilic protein kinases. Based on Hidaka's inhibitor H9, a generic fluorescent probe ARC-1083 was constructed possessing subnanomolar dissociation constant towards several kinases of the AGC-group. Thereafter, Hidaka's inhibitor HA1077 or Fasudil was conjugated with oligo-D-arginine resulting in the compound ARC-3002 revealing high affinity towards ROCK-II (K(d)=20 pM) and over 160-fold selectivity compared to PKAc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / chemistry*
  • Arginine / pharmacology
  • Isoquinolines / chemistry*
  • Isoquinolines / pharmacology
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology
  • rho-Associated Kinases / drug effects*


  • Isoquinolines
  • Sulfonamides
  • Arginine
  • rho-Associated Kinases