Phosphatase Screening Library

Phosphatases are enzymes that catalyze the dephosphorylation process. These enzymes replace a phosphate group on the substrate with a hydroxyl group from activation water. The action of phosphatases is directly opposite to that of phosphorylases and kinases. They play a significant role in signal transduction pathways and control a vast variety of cellular processes, including metabolism, gene transcription and translation, cell-cycle progression, cytoskeletal rearrangement, protein-protein interactions, protein stability, cell movement and apoptosis.

Applying similarity search method against reference compounds sets from ChEMBL and PubChem databases, Life Chemicals has designed its Phosphatase Screening Library of 2,735 small molecule compounds with predicted activity towards phosphatase targets, consisting of 2 parts.

Phosphatase Focused Library Part I (Similarity search against ChEMBL DB)

Using 2D fingerprints, generated with the Unity module of Sybyl-X, a Tanimoto similarity cut-off of 85 % was applied for screening of a reference set of known active compounds taken from the ChEMBL database.

All compounds in the reference set were chosen in accordance with accepted maximum activity value (IC50 < 1000 nM). In total, 3,395 unique compounds were included into the reference set for subsequent similarity search. As a result, over 594 similarcompounds were selected and added to the Library.

The list of targeted phosphatases:

  • Alkaline phosphatase tissue-nonspecific isozyme
  • Alkaline phosphatase placental-like
  • Dual specificity phosphatase Cdc25A
  • Dual specificity phosphatase Cdc25B
  • Dual specificity protein phosphatase 3
  • Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP
  • Intestinal alkaline phosphatase
  • Low molecular weight phosphotyrosine protein phosphatase
  • PH domain leucine-rich repeat-containing protein phosphatase 1
  • Phosphoethanolamine/phosphocholine phosphatase
  • Phosphotyrosine-protein phosphatase PTPB
  • Protein-tyrosine phosphatase 1B
  • Protein-tyrosine phosphatase 2C
  • Protein-tyrosine phosphatase LC-PTP
  • Receptor-type tyrosine-protein phosphatase O
  • Receptor-type tyrosine-protein phosphatase S

Phosphatase Focused Library Part II (Similarity search against PubChem, DrugBank, ChEBI DBs)

Based on a reference set of known 12,516 biologically active compounds (Activity (IC50, etc) ≤ 1 µM by PubChem) with proven potency in 88 phosphatase assays for the following 59 targets:

  • Acid phosphatase (Class B, ACP1, Purple)
  • ADP-sugar pyrophosphatase
  • Alkaline phosphatase (tissue-nonspecific isozyme, placental-like, ALPL, intestinal alkaline phosphatase)
  • Aspartate Phosphatase F
  • CTD small phosphatase 1
  • dCTP pyrophosphatase (DCTPP1, ASMTL)
  • Dual Specificity Phosphatase (CDC25 type A/B/C, PTEN, DUSP3)
  • Inositol monophosphatase
  • Inositol-1-phosphatase
  • Lipid-phosphate phosphatase
  • Low molecular weight phosphotyrosine protein phosphatase (ACP1, ets.)
  • PH domain leucine-rich repeat-containing protein phosphatase 1
  • Myosin light chain phosphatase
  • Phos Phosphatase Ahk4
  • Phosphoethanolamine/phosphocholine phosphatase
  • Phosphotyrosine-protein phosphatase PTPB
  • Tyrosine-protein phosphatase non-receptor type (SHP2, PTPN1, PTP1C, PTP2C, PTP4A3, LC-PTP, PTPN1, PTPN1, PTPN2, PTPN11, PTPN22, PTPN6, 70Z-PEP)
  • Protein-tyrosine phosphatase receptor type (PTPRA, PTPRC, PTPRD, PTPRE, PTPRF, PTPRO, PTPRS)
  • Protein-tyrosine phosphatase YopH
  • Pyridoxine 5'-phosphate phosphatase
  • Serine/threonine-protein phosphatase (PP1, PP2A, PP5, PP2C Abi1, PP2C HAB1, PP2C PH domain, PP1 Regulatory Subunit 71)
  • Undecaprenyl pyrophosphate phosphatase

The Life Chemicals HTS Compound Collection was searched for small molecules similar to the compounds included in the reference database using MDL public keys and the Tanimoto similarity cut-off 85 %. Ro5 compliance is indicated; reactive, toxic or PAINS compounds are excluded from the Library. As a result of this effort, 2,141 compounds were identified and added to the Library.