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

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Lavogina D, Kalind K, Bredihhina J, Hurt M, Vaasa A, Kasari M, Enkvist E, Raidaru G, Uri A

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.

PubMed ID

22521647 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Fasudil	Rho-associated protein kinase 2	IC 50 (nM)	11748.98	N/A	N/A	Details
Fasudil	Rho-associated protein kinase 2	Kd (nM)	78	N/A	N/A	Details