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Inhibition of tissue plasminogen activator (unknown origin) using GK-pNA as substrate preincubated for 10 mins followed by substrate addition measured for 30 mins by spectrophotometric analysis

PubChem AID
1225831
Primary Citation
Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases [PMID: 25782055]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
Status
Live
Dates
  • Deposit:
    2016-12-22
  • Modify:
    2020-06-24
Description
This bioassay record (AID 1225831) reports results from the above primary citation. Additional data from the same publication are reported in a total of 197 BioAssay records in PubChem.

1 Description

Title: Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases.

Abstract: The increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the β-lactam class of antimicrobials. A program was initiated to discover a new series of serine β-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine β-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria.

2 Comment

Journal: J Med Chem

Year: 2015

Volume: 58

Issue: 9

First Page: 3682

Last Page: 3692

DOI: 10.1021/acs.jmedchem.5b00127

Target ChEMBL ID: CHEMBL1873

ChEMBL Target Name: Tissue-type plasminogen activator

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 tissue plasminogen activator (unknown origin) using GK-pNA as substrate preincubated for 10 mins followed by substrate addition measured for 30 mins by spectrophotometric analysis

8.2 Source

8.3 External ID

8.4 Project Category

Literature, Extracted

8.5 BioAssay Type

Confirmatory

8.6 Deposit Date

2016-12-22

8.7 Modify Date

Version 1.1
Version 2.1
Version 2.2
2020-06-24 (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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