AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+) dependent. Structure-activity relationship studies indicated the presence of the 4-hydroxy group to be critical and selected substituted phenyl, polycyclic, and cycloaliphatic amides of xanthurenic acid to be well tolerated. ..more
Target
Sequence: RecName: Full=Platelet-activating factor acetylhydrolase; Short=PAF acetylhydrolase; AltName: Full=1-alkyl-2-acetylglycerophosphocholine esterase; AltName: Full=2-acetyl-1-alkylglycerophosphocholine esterase; AltName: Full=Group-VIIA phospholipase A2; Short=gVIIA-PLA2; AltName: Full=LDL-associated phospholipase A2; Short=LDL-PLA(2); AltName: Full=PAF 2-acylhydrolase; Flags: Precursor
Description ..
Comment ..
Gene:PLA2G7 Conserved Domain Related Protein 3D Structures
Description ..
Comment ..
Gene:PLA2G7 Conserved Domain Related Protein 3D Structures
Tested Compound:
Description:
Title: Amides of xanthurenic acid as zinc-dependent inhibitors of Lp-PLA(2).
Abstract: AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+) dependent. Structure-activity relationship studies indicated the presence of the 4-hydroxy group to be critical and selected substituted phenyl, polycyclic, and cycloaliphatic amides of xanthurenic acid to be well tolerated.
(PMID: 22217870)
Abstract: AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+) dependent. Structure-activity relationship studies indicated the presence of the 4-hydroxy group to be critical and selected substituted phenyl, polycyclic, and cycloaliphatic amides of xanthurenic acid to be well tolerated.
(PMID: 22217870)
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 10138
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 10138
ChEMBL target type: Target is a single protein chain
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Inhibition activity comment | Inhibition activity comment | String | |||
| 2 | Inhibition standard flag | Inhibition standard flag |  | Integer | ||
| 3 | Inhibition qualifier | Inhibition qualifier | String | |||
| 4 | Inhibition published value | Inhibition published value | | Float | ||
| 5 | Inhibition standard value | Inhibition standard value | | Float |
Data Table (Concise)
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