Inhibition of recombinant full length human CDK9/cyclin T expressed in baculovirus infected Sf9 insect cells using YSPTSPSYSPTSPSYSPTSPSKKKK as substrate in presence of [gamma-33P]ATP
- Deposit:2020-06-19
- Modify:2022-08-30
Title: Synthesis and anticancer activity of novel bisindolylhydroxymaleimide derivatives with potent GSK-3 kinase inhibition.
Abstract: Synthesis and biological evaluation of a series of novel indole derivatives as anticancer agents is described. A bisindolylmaleimide template has been derived as a versatile pharmacophore with which to pursue chemical diversification. Starting from maleimide, the introduction of an oxygen to the headgroup (hydroxymaleimide) was initially investigated and the bioactivity assessed by screening of kinase inhibitory activity, identifying substituent derived selectivity. Extension of the hydroxymaleimide template to incorporate substitution of the indole nitrogens was next completed and assessed again by kinase inhibition identifying unique selectivity patterns with respect to GSK-3 and CDK kinases. Subsequently, the anticancer activity of bisindolylmaleimides were assessed using the NCI-60 cell screen, disclosing the discovery of growth inhibitory profiles towards a number of cell lines, such as SNB-75 CNS cancer, A498 and UO-31 renal, MDA MB435 melanoma and a panel of leukemia cell lines. The potential for selective kinase inhibition by modulation of this template is evident and will inform future selective clinical candidates.
Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Journal: Bioorg Med Chem
Year: 2018
Volume: 26
Issue: 14
First Page: 4209
Last Page: 4224
DOI: 10.1016/j.bmc.2018.07.012
Target ChEMBL ID: CHEMBL2111389
ChEMBL Target Name: CDK9/cyclin T1
ChEMBL Target Type: PROTEIN COMPLEX - Target is a defined protein complex, consisting of multiple subunits
Relationship Type: D - Direct protein target assigned
Confidence: Direct protein complex subunits assigned
- PubChem
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