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Inhibition of ZAP70 (unknown origin) in presence of [gamma33P]ATP

PubChem AID
1291052
Primary Citation
Optimisation of a 5-[3-phenyl-(2-cyclic-ether)-methyl-ether]-4-aminopyrrolopyrimidine series of IGF-1R inhibitors [PMID: 26951753]
Source
External ID
BioAssay Type
Confirmatory
Tested Substances
Tested Compounds
Version
1.1
Status
Live
Dates
  • Deposit:
    2018-09-05
  • Modify:
    2018-09-05
Description
This bioassay record (AID 1291052) reports results from the above primary citation. Additional data from the same publication are reported in a total of 106 BioAssay records in PubChem.

1 Description

Title: Optimisation of a 5-[3-phenyl-(2-cyclic-ether)-methyl-ether]-4-aminopyrrolopyrimidine series of IGF-1R inhibitors.

Abstract: Taking the pyrrolopyrimidine derived IGF-1R inhibitor NVP-AEW541 as the starting point, the benzyl ether back-pocket binding moiety was replaced with a series of 2-cyclic ether methyl ethers leading to the identification of novel achiral [2.2.1]-bicyclic ether methyl ether containing analogues with improved IGF-1R activities and kinase selectivities. Further exploration of the series, including a fluorine scan of the 5-phenyl substituent, and optimisation of the sugar-pocket binding moiety identified compound 33 containing (S)-2-tetrahydrofuran methyl ether 6-fluorophenyl ether back-pocket, and cis-N-Ac-Pip sugar-pocket binding groups. Compound 33 showed improved selectivity and pharmacokinetics compared to NVP-AEW541, and produced comparable in vivo efficacy to linsitinib in inhibiting the growth of an IGF-1R dependent tumour xenograft model in the mouse.

2 Comment

Journal: Bioorg Med Chem Lett

Year: 2016

Volume: 26

Issue: 8

First Page: 2057

Last Page: 2064

DOI: 10.1016/j.bmcl.2016.02.075

Target ChEMBL ID: CHEMBL2803

ChEMBL Target Name: Tyrosine-protein kinase ZAP-70

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 ZAP70 (unknown origin) in presence of [gamma33P]ATP

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
2018-09-05 (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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