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Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay

PubChem AID
1290170
Primary Citation
Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods [PMID: 26878343]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
Status
Live
Dates
  • Deposit:
    2018-09-05
  • Modify:
    2022-08-30
Description
This bioassay record (AID 1290170) reports results from the above primary citation. Additional data from the same publication are reported in a total of 7 BioAssay records in PubChem.

1 Description

Title: Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods.

Abstract: Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins responsible for the regulation of programmed cell death. Amplification of Mcl-1 is a common genetic aberration in human cancer whose overexpression contributes to the evasion of apoptosis and is one of the major resistance mechanisms for many chemotherapies. Mcl-1 mediates its effects primarily through interactions with pro-apoptotic BH3 containing proteins that achieve high affinity for the target by utilizing four hydrophobic pockets in its binding groove. Here we describe the discovery of Mcl-1 inhibitors using fragment-based methods and structure-based design. These novel inhibitors exhibit low nanomolar binding affinities to Mcl-1 and >500-fold selectivity over Bcl-xL. X-ray structures of lead Mcl-1 inhibitors when complexed to Mcl-1 provided detailed information on how these small-molecules bind to the target and were used extensively to guide compound optimization.

2 Comment

Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Journal: J Med Chem

Year: 2016

Volume: 59

Issue: 5

First Page: 2054

Last Page: 2066

DOI: 10.1021/acs.jmedchem.5b01660

Target ChEMBL ID: CHEMBL4361

ChEMBL Target Name: Induced myeloid leukemia cell differentiation protein Mcl-1

ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain

Relationship Type: D - Direct protein target assigned

Confidence: Direct single protein target assigned

3 Result Definitions

4 Data Table

5 Target

8 Identity

8.1 BioAssay Name

Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2018-09-05

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 Type
Binding
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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