Human Phosphatases Annotated Library
Description
•Phosphatases are enzymatic proteins that dephosphorylate other functional proteins
•Physiologically the phosphatases enzymatic activity can be modulated by
-Catalytic phosphate site binders
-Allosteric binders that cause conformational changes within the catalytic site
•Phosphatases are interesting therapeutic targets for
-Oncology, e.g. cancer immunotherapy
-Metabolic diseases, e.g. diabetes, obesity
-Infections, e.g. antibacterial, antiviral
A unique collection of small molecule compounds with annotated activities for Phosphatases protein targets
- Annotated activities : 25 phosphatase targets
- Express Delivery : 160 compounds
- Complete Version : 225 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 |
|
H025-3231 |
O14976 |
Serine/threonine-protein kinase GAK |
Kd |
= |
2700 |
nM |
22037378 |
10.1038/nbt.1990 |
|
Cyclin-G-associated kinase |
Binding constant for GAK kinase domain |
|
Y203-7358 |
P34913 |
Epoxide hydratase |
IC50 |
= |
700 |
nM |
19746975 |
10.1021/jm9005302 |
|
Bifunctional epoxide hydrolase 2 |
Displacement of rhodamine-labeled probe from human soluble epoxide hydrolase by fluorescence polarization assay |
|
7547-4118 |
P05186 |
Alkaline phosphatase tissue-nonspecific isozyme |
IC50 |
= |
1130 |
nM |
19821572 |
10.1021/jm900383s |
|
Alkaline phosphatase tissue-nonspecific isozyme |
Inhibition of TNAP transfected in african green monkey COS1 cells by colorimetric assay |
|
4032-1302 |
Q13822 |
Autotaxin |
IC50 |
= |
56 |
nM |
20536182 |
10.1021/jm1005012 |
|
Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 |
Inhibition of 6x-histidine-tagged human recombinant ATX expressed in HEK293 cells using bisP-nitrophenyl phosphate as a substrate |
|
8005-8111 |
P08575 |
Leukocyte common antigen |
IC50 |
= |
700 |
nM |
11356112 |
10.1021/jm000447i |
|
Receptor-type tyrosine-protein phosphatase C |
In vitro inhibitory activity against the cytosolic portion of CD45 protein-tyrosine phosphatase using pNPP as the substrate |
|
R092-0051 |
Q13332 |
Receptor-type tyrosine-protein phosphatase S |
IC50 |
= |
4300 |
nM |
26602279 |
10.1016/j.bmcl.2015.11.026 |
|
Receptor-type tyrosine-protein phosphatase S |
Inhibition of recombinant human PTP-sigma (residues 1367 to 1948) using para-nitrophenylphosphate as substrate for 60 mins by fluorescence analysis |
|
4489-1466 |
O75365 |
Protein-tyrosine phosphatase 4A3 |
IC50 |
= |
1100 |
nM |
23726031 |
10.1016/j.bmcl.2013.04.092 |
|
Protein tyrosine phosphatase type IVA 3 |
Inhibition of human His6-tagged full length PRL3 assessed as inhibition of DiFMUP dephosphorylation |
|
0111-0158 |
P34913 |
Epoxide hydratase |
IC50 |
= |
1.6 |
nM |
22079754 |
10.1016/j.bmcl.2011.10.074 |
|
Bifunctional epoxide hydrolase 2 |
Inhibition of human soluble epoxide hydrolase using CMNPC as substrate after 5 mins by fluorescent assay |
|
2817-4329 |
P18031 |
Protein-tyrosine phosphatase 1B |
Ki |
= |
3000 |
nM |
21420867 |
10.1016/j.bmc.2011.02.047 |
|
Tyrosine-protein phosphatase non-receptor type 1 |
Inhibition of PTP1B |
Publications
1.J. Med. Chem. 2009 52(21):6716-6723. Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells. Wu S Vossius S Rahmouni S Miletic AV Vang T Vazquez-Rodriguez J Cerignoli F Arimura Y Williams S Hayes T Moutschen M Vasile S Pellecchia M Mustelin T Tautz L.2.J. Med. Chem. 2001 44(24):4042-4049. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25. Lazo JS Aslan DC Southwick EC Cooley KA Ducruet AP Joo B Vogt A Wipf P.
3.J. Med. Chem. 2017 60(18):7703-7724. A Dual Modulator of Farnesoid X Receptor and Soluble Epoxide Hydrolase To Counter Nonalcoholic Steatohepatitis. Schmidt J Rotter M Weiser T Wittmann S Weizel L Kaiser A Heering J Goebel T Angioni C Wurglics M Paulke A Geisslinger G Kahnt A Steinhilber D Proschak E Merk D.
4.Bioorg. Med. Chem. Lett. 2009 19(1):222-225. Design and synthesis of pyrazole derivatives as potent and selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). Sidique S Ardecky R Su Y Narisawa S Brown B Millán JL Sergienko E Cosford ND.
5.J. Med. Chem. 2009 52(21):6919-6925. Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). Dahl R Sergienko EA Su Y Mostofi YS Yang L Simao AM Narisawa S Brown B Mangravita-Novo A Vicchiarelli M Smith LH O'Neill WC Millán JL Cosford ND.
6.Bioorg. Med. Chem. Lett. 2006 16(19):5212-5216. Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase. Jones PD Tsai HJ Do ZN Morisseau C Hammock BD.
7.Bioorg. Med. Chem. Lett. 2009 19(8):2240-2243. Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the 138-triazaspiro[45]decan-4-one privileged structure that engenders PLD2 selectivity. Lavieri R Scott SA Lewis JA Selvy PE Armstrong MD Alex Brown H Lindsley CW.