This compound is also called ROCK-IN-2, Azaindole 1, Azaindole 1, TC-5 7001 and the CAS No. is 867017-68-3
Schirok et al ChemMedChem 3 (2008) 1893 – 1904 (Cmpd 32)
SAR development? Yes, clear SAR with optimization.
ROCK-2 IC50 is given as 3 nM.
Arteria saphena IC50 65 nM (functional, rabbit) SAR approximately parallels kinase SAR.
Biomarker pMBS not undertaken.
Medium clearance mice and dogs; t1/2 rats 1.2 h, F 48%.
Kast et al BJP 152 (2020) 1070-1080
IC50 ROCK-1 is given as 0.6 nM.
Functional inhibition: IC50 (pMBS, human) is given as 3.7 nM.
IC50 ROCK-2 is given as 1.1 nM.
Functional inhibition: IC50 (pMBS, human) is given as 4.8 nM.
The compound is ATP-competitive.
Inactive against 89 kinases (IC50 > 10uM), another 21 weakly inhibited with IC50 1-10 uM, only 2 sub-uM IC50 (TRK 252 nM, FLT3 303 nM).
Inactive against 60 relevant cardiovascular enzymes/receptors and weak activity just against L-type calcium channel (6.7 uM) and sodium channel (6.8 uM).
Highly bioavailable rats, dogs (approximately 50%-75%).
28 Jun 2020 )