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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

PubChem AID
1397572
Primary Citation
Synthesis and anticancer activity of novel bisindolylhydroxymaleimide derivatives with potent GSK-3 kinase inhibition [PMID: 30026041]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
Status
Live
Dates
  • Deposit:
    2020-06-19
  • Modify:
    2022-08-30
Description
This bioassay record (AID 1397572) reports results from the above primary citation. Additional data from the same publication are reported in a total of 389 BioAssay records in PubChem.

1 Description

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.

2 Comment

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

3 Result Definitions

4 Data Table

5 Target

2 of 2
Protein Target

8 Identity

8.1 BioAssay Name

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

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2020-06-19

8.7 Modify Date

Version 1.1
Version 1.2
2022-08-30 (currently shown)

8.8 Status

Live

9 Same-Publication BioAssays

10 BioAssay Annotations

Assay Format
Cell-based
Assay Type
Binding
Assay Cell Type
Sf9
Assay Organism

11 Information Sources

  1. PubChem
  2. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
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