Human Proteases Annotated Library
Description
•Proteases are enzymatic proteins that cleave specific peptide bonds withing other functional proteins
•Physiologically the protease enzymatic activity can be modulated by
-Mimetics of peptide motifs that bind at a catalytic site
-Chelators of specific metal ions that often used by proteases as cofactors
•Proteases are well recognized as important therapeutic targets for
-Infections, e.g. antibacterial, antiviral, antimalarials
-Inflammatory diseases, e.g. fibrosis, NSAID painkillers, joint stiffness
-Cardiovascular system, e.g. blood pressure regulation, thrombosis
A unique collection of small molecule compounds with annotated activities for Proteases protein targets
- Annotated activities : 60 protease targets
- Express Delivery : 320 compounds
- Complete Version : 2976 compounds
Library Composition
Data sources of annotations : Pharos, ChEMBL 25, PubChem, PubMed, Current Patent Literature (CAS, Integrity)
IDNUMBER – ChemDiv Catalog ID (in some instances the same IDNUMBER might have multiple annotation entries due to multiple data sources or because having activity against multiple similar targets);
UNIPROT – SwissProt and ChEMBL Target accesion ID;
Type – character of the measured activity;
Value – Active compounds selection criteria, included only compounds with reported activities < 5 µM;
pubmed_id – PubMed record entry;
doi, patent_id – journal or patent reference to a publication of original data;
For screening data extracted from PubChem, see column assay_description for entry names PUBCHEM_BIOASSAY
Example of Annotations - an Excel file structure
|
IDNUMBER |
UNIPROT |
Target Name |
Type |
Relation |
Value |
Units |
pubmed_id |
doi |
patent_id |
Target Description |
assay_description |
|
8010-3886 |
P05981 |
Serine protease hepsin |
IC50 |
= |
430 |
nM |
|
|
US-9182402-B2 |
Serine protease hepsin |
High-Throughput Screening Assay: To identify novel inhibitors of hepsin (Zhang et al. 1999 J Biomol Screen 4:67) |
|
C050-0376 |
P07858 |
Cathepsin B |
IC50 |
= |
690 |
nM |
17656088 |
10.1016/j.bmcl.2007.06.091 |
|
Cathepsin B |
Inhibition of human liver cathepsin B |
|
R152-2078 |
P15144 |
Aminopeptidase N |
IC50 |
= |
30 |
nM |
7909847 |
10.1021/jm00035a014 |
|
Aminopeptidase N |
Inhibitory potency against aminopeptidase N (APN) |
|
K839-0145 |
Q9UNA0 |
ADAMTS5 |
IC50 |
= |
830 |
nM |
18974001 |
10.1016/j.bmcl.2008.10.065 |
|
A disintegrin and metalloproteinase with thrombospondin motifs 5 |
Inhibition of ADAMTS5 by FRET assay |
|
P160-0032 |
P42574 |
Caspase-3 |
IC50 |
= |
23 |
nM |
15916416 |
10.1021/jm048987t |
|
Caspase-3 |
In vitro inhibitory concentration against human caspase-3 |
|
4487-0140 |
P00749 |
Urokinase-type plasminogen activator |
IC50 |
= |
170 |
nM |
17850059 |
10.1021/jm070600+ |
|
Urokinase-type plasminogen activator |
Inhibition of human urokinase |
|
3375-0321 |
P08253 |
Matrix metalloproteinase-2 |
IC50 |
= |
302 |
nM |
|
|
|
72 kDa type IV collagenase |
PUBCHEM_BIOASSAY: Dose Response validation of uHTS RPN11 inhibitor hits using a MMP-2 Fluorescence assay. (Class of assay: confirmatory) |
|
3229-1443 |
P45452 |
Matrix metalloproteinase 13 |
IC50 |
= |
640 |
nM |
|
10.1039/C4MD00556B |
|
Collagenase 3 |
Inhibition of MMP13 (unknown origin) using Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate |
|
V030-2981 |
P42892 |
Endothelin-converting enzyme 1 |
IC50 |
= |
220 |
nM |
16085415 |
10.1016/j.bmcl.2005.06.085 |
|
Endothelin-converting enzyme 1 |
Inhibitory concentration against endothelin converting enzyme 1 using bradykinin-derived substrate |
|
8015-0649 |
P43235 |
Cathepsin K |
IC50 |
= |
400 |
nM |
23350811 |
10.1021/jm3013932 |
|
Cathepsin K |
Inhibition of human recombinant His-tagged cathepsin K using Cbz-Phe-Arg-AMC as substrate |
|
4234-0237 |
P00748 |
Coagulation factor XII |
IC50 |
|
533 |
nM |
|
|
|
Coagulation factor XII |
PUBCHEM_BIOASSAY: Factor XIIa 1536 HTS Dose Response Confirmation. (Class of assay: confirmatory) |
Publications
1.J. Med. Chem. 2007 50(20):4928-4938. N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. Schepetkin IA Khlebnikov AI Quinn MT.
2.J. Med. Chem. 2000 43(9):1793-1806. Protease inhibitors: synthesis and QSAR study of novel classes of nonbasic thrombin inhibitors incorporating sulfonylguanidine and O-methylsulfonylisourea moieties at P1. Supuran CT Scozzafava A Briganti F Clare BW.
3.J. Med. Chem. 2009 52(10):3212-3224. Exploration of structure-activity relationship determinants in analogue series. Peltason L Weskamp N Teckentrup A Bajorath J.
4.ACS Med. Chem. Lett. 2013 4(8):699-703. Discovery of Inhibitors of Burkholderia pseudomallei Methionine Aminopeptidase with Antibacterial Activity. Wangtrakuldee P Byrd MS Campos CG Henderson MW Zhang Z Clare M Masoudi A Myler PJ Horn JR Cotter PA Hagen TJ.
5.Bioorg Med Chem 2017 25(3):813-824. Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents. Helgren TR Chen C Wangtrakuldee P Edwards TE Staker BL Abendroth J Sankaran B Housley NA Myler PJ Audia JP Horn JR Hagen TJ.
6.Bioorg. Med. Chem. Lett. 1999 9(17):2531-2536. Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors. Dumas J Brittelli D Chen J Dixon B Hatoum-Mokdad H König G Sibley R Witowsky J Wong S.
7.J. Med. Chem. 2014 57(22):9598-9611. Characterization of selective exosite-binding inhibitors of matrix metalloproteinase 13 that prevent articular cartilage degradation in vitro. Spicer TP Jiang J Taylor AB Choi JY Hart PJ Roush WR Fields GB Hodder PS Minond D.
8.MedChemComm 2015 6(5):823-830. Evaluation of the anti-inflammatory/chondroprotective activity of aldose reductase inhibitors in human chondrocyte cultures. Panico A Maccari R Cardile V Avondo S Crasci L Ottana R
9.ACS Med. Chem. Lett. 2013 4(6):565-569. Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold. Mori M Massaro A Calderone V Fragai M Luchinat C Mordini A.