Disease relevance of DPP9

• As off-target inhibitions of DPP8 and/or DPP9 have shown profound toxicities in the in vivo studies, it is important to develop selective DPP-IV inhibitors for clinical usage [1].

High impact information on DPP9

• Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9 [2].
• Northern-blot analysis shows that whereas DPP8 and DPP9 are widely expressed, DPP10 is expressed mainly in the brain and pancreas [3].
• A DPP9 orthologue in mice was identified by expressed sequence tag database searches and verified by cDNA cloning [4].
• Lack of selectivity toward the related enzymes DP8 and DP9 has recently emerged as a possible source of drug-induced toxicity [5].
• Dipeptidyl peptidase 9-overexpressing cells exhibited impaired cell adhesion, migration in transwells and monolayer wound healing on collagen I, fibronectin and Matrigel [6].

Biological context of DPP9

• Extraenzymatic functions of the dipeptidyl peptidase IV-related proteins DP8 and DP9 in cell adhesion, migration and apoptosis [6].
• The effects of dipeptidyl peptidase 8 and dipeptidyl peptidase 9 on cell adhesion, cell migration, wound healing and apoptosis were measured by using green fluorescent protein fusion proteins to identify transfected cells [6].
• Mechanistic investigations showed that neither the catalytic serine of dipeptidyl peptidase 8 or dipeptidyl peptidase 9 nor the Arg-Gly-Asp integrin-binding motif in dipeptidyl peptidase 9 were required for the impairment of cell survival, cell adhesion or wound healing [6].
• DPP8 and DPP9 share an identical active site with DPP4 (Gly-Trp-Ser-Tyr-Gly) [3].
• The deduced amino acid sequence of DPP9 has a serine protease motif, GWSYG, identical to that found in DPP IV [4].

Associations of DPP9 with chemical compounds

• The trifluoroacetate salt form of ER-319711, ER-319711-15, inhibited human DPP-IV with an IC(50) value of 0.089 muM, whereas its IC(50) values toward human DPP8 and DPP9 were >100 muM [7].
• anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9 [8].

Other interactions of DPP9

• This is the first demonstration that dipeptidyl peptidase 8 and dipeptidyl peptidase 9 influence cell-extracellular matrix interactions, and thus may regulate tissue remodeling [6].
• DP9 exhibited post-proline dipeptidyl aminopeptidase activity and was a cytoplasmic, 110-kDa monomer [9].

References