Appendix Table 2. .
Cross-Target Query of PubChem With Redox Cycling Compounds (RCCs) Against Oxidation-Sensitive Targets
|
Target |
|
MKP-1 |
MKP-3 |
Cdc25B |
Caspase 1 |
Caspase 7 |
Cathepsin L |
Cathepsin B |
Hsp90 |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AID |
RCC |
374 |
551 |
425 |
553 |
368 |
569 |
900 |
900 |
897 |
897 |
460 |
825 |
453 |
820 |
429 |
712 |
| SID | AC50 μM | HTS Active | Conf. active | HTS Active | Conf. active | HTS Active | Conf. active | HTS Active | Conf. active | HTS Active | Conf active | HTS Active | Conf active | HTS Active | Conf. active | HTS Active | Conf. active |
| 14727570 | <0.01 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14727734 | 0.19 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 22404392 | 0.43 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 16952991 | 0.72 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14723875 | 0.9 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 845167 | 0.9 | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| 11532976 | 1.48 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 24809205 | 1.51 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 24814503 | 2.73 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14726526 | 2.76 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14730721 | 2.88 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 24809506 | 3.11 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14742005 | 6.44 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 847359 | 7.85 | No | No | Yes | Yes | NT | No | No | No | Yes | Yes | ||||||
| 17507336 | 9.42 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14719117 | 9.85 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17508465 | 11.77 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17511877 | 12.27 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17510947 | 12.5 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 22405508 | 12.84 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 24812833 | 12.87 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17510616 | 12.98 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14727791 | 18.44 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14742458 | 19.15 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17510946 | 23.26 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 24813200 | 24.03 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14742370 | 26.04 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 22400632 | 28.27 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 857446 | 28.18 | No | No | No | IC | NT | No | No | No | ||||||||
| 17433753 | 34.04 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 22412622 | 38.24 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17516177 | 39.24 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17513322 | 40.61 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17504835 | 40.9 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 17505825 | 41.24 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 24825938 | 45.23 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
| 14742003 | 48.41 | NT | NT | NT | NT | NT | NT | NT | NT | ||||||||
We queried the PubChem database for the cross-target bioactivity profiles of the Redox Cycling Compounds (RCCs) against a subset of 8 targets that are known to be sensitive to oxidation: the protein tyrosine phosphatases (PTPs), mitogen-activated protein kinase phosphatase 1 (MKP-1) and 3 (MKP-3), cell division cycle 25 homolog B (Cdc25B); the cysteine proteases Cathepsin L, Cathepsin B, Caspase 1, and Caspase 7; and the heat shock protein 90 (Hsp90). The PubChem substance identifier (SID) number of each compound was used to query the PubChem database to determine if the compound had been tested in the specific target primary HTS assay, data accessed via the assay identifier (AID), if it was active in the primary screen, and if it had been confirmed active in a concentration-dependent assay. A designation of NT in the HTS activity column (HTS-active) indicates that the compound was not tested in the primary HTS. A compound that was tested and considered active in the primary screen was indicated by a Yes in the HTS activity column, and a compound that was tested and considered inactive in the primary screen was indicated by a No in the HTS activity column. A compound that was tested and considered inconclusive in the primary screen was indicated by an IC in the HTS activity column. Compounds that were confirmed active in a concentration-dependent assay were indicated with a Yes in the confirmed active (Conf. active) column. The RCC AC50 (μM) is the 50% effective concentration of activation of H2O2 generation in presence of 0.8 mM DTT for that PubChem-SID.
Abbreviations: AID, PubChem Assay Identifier; SID, PubChem Substance Identity Number.