Summary assay for identification of inhibitors of mouse intestinal alkaline phosphatase
Alkaline phosphatase (EC 220.127.116.11) (APs) catalyze the hydrolysis of phosphomonoesters, releasing inorganic phosphate and alcohol. APs are dimeric enzymes found in most organisms. In human, four isozymes of APs have been identified. One isozyme is tissue-nonspecific (designated TNAP) and three other isozymes are tissue-specific and named according to the tissue of their predominant expression: more ..
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Probe Production Centers Network (MLPCN)
Grant Proposal Number: X01-MH077602-01
Assay Provider: Dr. Jose Luis Millan, Sanford-Burnham Medical Research Institute, San Diego, CA.
Alkaline phosphatase (EC 18.104.22.168) (APs) catalyze the hydrolysis of phosphomonoesters, releasing inorganic phosphate and alcohol. APs are dimeric enzymes found in most organisms. In human, four isozymes of APs have been identified. One isozyme is tissue-nonspecific (designated TNAP) and three other isozymes are tissue-specific and named according to the tissue of their predominant expression: intestinal (IAP), placental (PLAP) and germ cell (GCAP) alkaline phosphatases. IAP expression is largely restricted to the gut, especially to the epithelial cells (enterocytes) of the small intestinal mucosa. The exact biological function of IAP is unknown.
The goal of this project is to identify novel and specific inhibitors of mouse IAP. IAP is inhibited by a number of inhibitors (1). They include L-phenylalanine, (2, 3), L-tryptophan (4), L-leucine and phenylalanine-glycylglycine (5). While the biological implications of this inhibition are not known, these inhibitors have proven to be useful in the differential determination of AP isozymes as important diagnostic markers in many diseases. However, these known inhibitors of IAP are not entirely specific for IAP isozyme and have milllimolar affinity. In addition, they are common aminoacids that are ubiquitously present in the tissues and involved in diverse metabolic pathways, and therefore, are not appropriate tools for biological studies. Thus, the aim of this MLSCN probe project is to obtain novel chemical scaffolds that can be used as chemical probes.
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML260
PubChem Substance ID (SID) for probe 1: 124756790
PubChem Compound ID (CID) for probe 1: 50919367
Probe type for probe 1: Inhibitor
IC50/EC50 (nM) for probe 1: 540
Target for probe 1: muIAP inhibitor (mouse) (gi: 124487323)
Disease relevance for probe 1: Cystic Fibrosis
Anti-target for probe 1: TNAP Inhibitor; PLAP Inhibitor; huIAP (human) Inhibitor
Fold selectivity for probe 1: >35
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK143562/ (ID: 3036550)
Grant number for probe 1: MH077602-01
NCBI Book chapter title for probe 1: A Selective Murine Intestinal Alkaline Phosphatase (muIAP) Inhibitor