compound 101 [PMID: 21596927]

Ligand id: 8437

Name: compound 101 [PMID: 21596927]

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 84.73
Molecular weight 466.17
XLogP 6.01
No. Lipinski's rules broken 1

Molecular properties generated using the CDK

View interactive charts of activity data from ChEMBL and GtoPdb across species (New!)

Bioactivity Comments
Compound 101 is selective for the GRK2 subfamily (GRK2 and GRK3) of G protein-coupled receptor kinases [3]. Subsequent profile screening (of 58 kinases representative of the entire kinome, excl. lipid kinases) identifies only 5 off-target kinases inhibited by compound 101 by >50% (@ 1μM): protein kinase C related protein kinase (PRK2), serum and glucocorticoid regulated kinase (SGK1), ribosomal protein S6 kinase, 90kDa, polypeptide 1 (RSK1) , ribosomal protein S6 kinase, 90kDa, polypeptide 5 (MSK1) and ribosomal protein S6 kinase, 70kDa, polypeptide 1 (S6K1) [2].
A role for these GPCR-related kinases in desensitisation of activated μ opioid receptors is identified by experiments showing that compound 101-induced inhibition of GRK2/3 partially reverses agonist-induced desensitisation of the μ opioid receptor [2].
Selectivity at human enzymes
Key to terms and symbols Click column headers to sort
Target Type Action Affinity Units Concentration range (M) Reference
beta adrenergic receptor kinase 2 Inhibitor Inhibition 7.5 pIC50 - 3
pIC50 7.5 (IC50 3.2x10-8 M) [3]
beta adrenergic receptor kinase 1 Inhibitor Inhibition 7.3 pIC50 - 3
pIC50 7.3 (IC50 5.4x10-8 M) [3]