General
Preferred name
BAY-549
Synonyms
TC-S 7001 ()
Azaindole 1 ()
ROCK inhibitor ()
BAY549 ()
ROCK-IN-2 ()
Azaindole 1 (TC-S 7001) ()
TC-S 7001 ()
Azaindole-1 ()
P&D ID
PD069579
CAS
867017-68-3
Tags
available
free of charge
probe
Probe info
Probe type
P&D approved
experimental probe
Probe selectivity
family-selective
Probe sources
Chemical Probes.org
High-quality chemical probes
Open Science Probes
Probe targets
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
COMMENT The selectivity screening only included 112 kinases, data not supplied. It is possible that wider screening would identify additional inhibited kinases, albeit that the closest relatives to ROCK1 and ROCK2 (MRCKs) have only ~38% sequence identity over the kinase domain. Jun 7 2020 - 10:34am; 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%). Jun 28 2020 - 9:08am; BAY-549, also known as compound 32 in Schirok H, et al ChemMedChem 2008, or Azaindole 1 in Kast R, et al  Br J Pharmacol 2007, is a high quality tool compound for ROCK1/2. It is active in rabbit isolated artery assay and reduces blood pressure when dosed in rats and dogs. The only limitation is that kinome selectivity data are limited to a panel of 112 kinases (Upstate), so it remains possible that the compound may have off-target kinase activities outside the tested panel.  That said, ROCK1/2 kinases have unique active site structure as noted in the paper, so this is an unlikely scenario. Regardless, it would be prudent to test multiple  ROCK1/2 inhibitors from orthogonal chemical scaffolds, for example also GSK429286A (https://lincs.hms.harvard.edu/db/datasets/20030/main).  Mar 24 2021 - 10:18am
DESCRIPTION BAY-549 (Azaindole 1) is an orally active and ATP-competitive ROCK inhibitor with IC50s of 0.6 and 1.1 nM for human ROCK-1 and ROCK-2, respectively[1].
PRICE 395
MOA Inhibitor (Chemical Probes.org)
DESCRIPTION ROCK-IN-2 (Azaindole 1) is a selective and ATP-competitive ROCK inhibitor with IC50 of 0.6 and 1.1 nM for human ROCK-1 and ROCK-2. (TargetMol Bioactive Compound Library)
Cell lines
20
Organisms
0
Compound Sets
10
AdooQ Bioactive Compound Library
A15225
Cayman Chemical Bioactives
19129
Chemical Probes.org
bay-549
CZ-OPENSCREEN Bioactive Library
EUbOPEN Chemogenomics Library
EUB0000716
High-quality chemical probes
PD069579
MedChem Express Bioactive Compound Library
HY-10319
Open Science Probes
BAY-549
Selleckchem Bioactive Compound Library
azaindole-1
TargetMol Bioactive Compound Library
TQ0110
External IDs
13
Properties
(calculated by RDKit )
Molecular Weight
402.08
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
3
Rotatable Bonds
4
Ring Count
4
Aromatic Ring Count
4
cLogP
4.71
TPSA
101.74
Fraction CSP3
0.06
Chiral centers
0.0
Largest ring
6.0
QED
0.43
Structural alerts
0
No structural alerts detected
Custom attributes
(extracted from source data)
Target
ROCK
ROCK1
ROCK2
ROCK1, ROCK2
MOA
Inhibitor
Protein Family
Kinase catalytic domain
Target subclass
AGC
AGC, AGC
Target class
Protein kinase
Kinase, Kinase
Pathway
Cell Cycle/DNA Damage
cytoskeleton
Stem Cell/Wnt
TGF-beta/Smad
Cell Cycle/Checkpoint
Cytoskeletal Signaling
Stem Cells
Control name
BAY-4900
Recommended Cell Concentration
100 nM
Source data