note: The Chemical Probes Portal only endorses
compounds as chemical probes for use as specific and
selective modulators of the proposed target if they
receive three or more (3-4) stars.
PDB ID for probe-target interaction (3D structure):
3OCS
Structure-activity relationship:
Hit-to-lead chemistry confirmed the importance of the hydrogen bond donor-acceptor arrangement provided by the amino-imidazopyrazine, identified bioisosteric hinge binding motifs and highlighted the para position of the 8-aniline ring as a promiscuous site tolerant of diverse substitutions. Notably, we found the t-butylphenyl amide to be a critical pharmacophore for potency and selectivity.
Potency assay (off target):
CGI1746 is ~1,000-fold selective over the next kinase in Ambit KinomeScan of 385 kinases and UBI Kinase Profiler of 205 kinases.
Probe Selectivity in
Vitro:
Against 82 non-kinase targets, CGI1746 showed <40% inhibition at 1 uM for all targets, and <15% inhibition for 78 of them.
