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Inhibition of AKR1C3-mediated [14C]farnesal metabolism in human MCF7 cells incubated for 2 hrs prior to substrate addition measured after 6 hrs

PubChem AID
664564
Primary Citation
Selective inhibition of human type-5 17β-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis [PMID: 22506594]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
Status
Live
Dates
  • Deposit:
    2013-05-16
  • Modify:
    2022-08-30
Description
This bioassay record (AID 664564) reports results from the above primary citation. Additional data from the same publication are reported in a total of 32 BioAssay records in PubChem.

1 Description

Title: Selective inhibition of human type-5 17β-hydroxysteroid dehydrogenase (AKR1C3) by baccharin, a component of Brazilian propolis.

Abstract: The human aldo-keto reductase (AKR) 1C3, also known as type-5 17β-hydroxysteroid dehydrogenase and prostaglandin F synthase, has been suggested as a therapeutic target in the treatment of prostate and breast cancers. In this study, AKR1C3 inhibition was examined by Brazilian propolis-derived cinnamic acid derivatives that show potential antitumor activity, and it was found that baccharin (1) is a potent competitive inhibitor (K(i) 56 nM) with high selectivity, showing no significant inhibition toward other AKR1C isoforms (AKR1C1, AKR1C2, and AKR1C4). Molecular docking and site-directed mutagenesis studies suggested that the nonconserved residues Ser118, Met120, and Phe311 in AKR1C3 are important for determining the inhibitory potency and selectivity of 1. The AKR1C3-mediated metabolism of 17-ketosteroid and farnesal in cancer cells was inhibited by 1, which was effective from 0.2 μM with an IC(50) value of about 30 μM. Additionally, 1 suppressed the proliferation of PC3 prostatic cancer cells stimulated by AKR1C3 overexpression. This study is the first demonstration that 1 is a highly selective inhibitor of AKR1C3.

2 Comment

Journal: J Nat Prod

Year: 2012

Volume: 75

Issue: 4

First Page: 716

Last Page: 721

DOI: 10.1021/np201002x

Target ChEMBL ID: CHEMBL4681

ChEMBL Target Name: Aldo-keto-reductase family 1 member C3

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

Inhibition of AKR1C3-mediated [14C]farnesal metabolism in human MCF7 cells incubated for 2 hrs prior to substrate addition measured after 6 hrs

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2013-05-16

8.7 Modify Date

Version 1.1
Version 2.1
Version 3.1
Version 4.1
Version 5.1
Version 5.2
Version 5.3
Version 5.4
Version 5.5
Version 6.1
Version 6.2
Version 7.1
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
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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