Merops Switch to
Inhibitors

Peptidase

Family Clan SEARCHES BLAST
MEROPS SUBMISSIONS

Other
information

Literature for peptidase S09.018: dipeptidyl-peptidase 8

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Pharma

(Topics flags: S Structure, R Splicing, P Specificity, I Inhibitor, E Expression, V Review. To select only the references relevant to a single topic, click the link above. See explanation.)

    2025
  1. Ahmad,S.S., Ahmed,F., Ahmad,S., Krishnan,A. and Khan,M.A.
    Targeting dipeptidyl peptidase-8/9 to combat inflammation-induced osteoclastogenesis in RAW264.7 macrophages and analysis of anti-osteoclastogenesis potential of chrysin
    Iran J Basic Med Sci28, 516-526. PubMed  Europe PubMed DOI
    2. 2024
  2. Espadinha,M., De Loose,J., Corthaut,S., Thys,S., Van Rymenant,Y., Verhulst,E., Benramdane,S., Filippi,N., Augustyns,K., Van Wielendaele,P., Pintelon,I., De Meester,I. and Van der Veken,P.
    Active site-directed probes targeting dipeptidyl peptidases 8 and 9
    Eur J Med Chem270, 116389-116389. PubMed  Europe PubMed DOI
    3. 2023
  3. Donzelli,L., Bolgi,O. and Geiss-Friedlander,R.
    The amino-dipeptidyl peptidases DPP8 and DPP9: Purification and enzymatic assays
    Methods Enzymol684, 289-323. PubMed  Europe PubMed DOI
    4. 2022
  4. Benramdane,S., De Loose,J., Beyens,O., Van Rymenant,Y., Vliegen,G., Augustyns,K., De Winter,H., De Meester,I. and Van der Veken,P.
    Vildagliptin-Derived Dipeptidyl Peptidase 9 (DPP9) Inhibitors: Identification of a DPP8/9-Specific Lead
    ChemMedChem17, e202200097-e202200097. PubMed  Europe PubMed DOI  I
  5. Cui,C., Tian,X., Wei,L., Wang,Y., Wang,K. and Fu,R.
    New insights into the role of dipeptidyl peptidase 8 and dipeptidyl peptidase 9 and their inhibitors
    Front Pharmacol13, 1002871-1002871. PubMed  Europe PubMed DOI  V
    6. 2021
  6. Hollingsworth,L.R., Sharif,H., Griswold,A.R., Fontana,P., Mintseris,J., Dagbay,K.B., Paulo,J.A., Gygi,S.P., Bachovchin,D.A. and Wu,H.
    DPP9 sequesters the C terminus of NLRP1 to repress inflammasome activation
    Nature PubMed  Europe PubMed DOI
  7. Sharif,H., Hollingsworth,L.R., Griswold,A.R., Hsiao,J.C., Wang,Q., Bachovchin,D.A. and Wu,H.
    Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment
    Immunity PubMed  Europe PubMed DOI
    8. 2019
  8. de Vasconcelos,N.M., Vliegen,G., Goncalves,A., De Hert,E., Martin-Perez,R., Van Opdenbosch,N., Jallapally,A., Geiss-Friedlander,R., Lambeir,A.M., Augustyns,K., Van der Veken,P., De Meester,I. and Lamkanfi,M.
    DPP8/DPP9 inhibition elicits canonical Nlrp1b inflammasome hallmarks in murine macrophages
    Life Sci Alliance2, PubMed  Europe PubMed DOI  I
  9. Griswold,A.R., Cifani,P., Rao,S.D., Axelrod,A.J., Miele,M.M., Hendrickson,R.C., Kentsis,A. and Bachovchin,D.A.
    A chemical strategy for protease substrate profiling
    Cell Chem Biol26, 901-907. PubMed  Europe PubMed DOI
    10. 2018
  10. Ross,B., Krapp,S., Augustin,M., Kierfersauer,R., Arciniega,M., Geiss-Friedlander,R. and Huber,R.
    Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer
    Proc Natl Acad Sci U S A115, E1437-E1437. PubMed  Europe PubMed DOI  S
    11. 2017
  11. Okondo,M.C., Johnson,D.C., Sridharan,R., Go,E.B., Chui,A.J., Wang,M.S., Poplawski,S.E., Wu,W., Liu,Y., Lai,J.H., Sanford,D.G., Arciprete,M.O., Golub,T.R., Bachovchin,W.W. and Bachovchin,D.A.
    DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis
    Nat Chem Biol13, 46-53. PubMed  Europe PubMed DOI  I
    12. 2016
  12. Heirbaut,L., VanGoethem,S., Jansen,K., DeWinter,H., Lamoen,N., Joossens,J., Cheng,J., Chen,X., Lambeir,A.-M., DeMeester,I., Augustyns,K. and VanDer Veken,P.
    Probing for improved selectivity with dipeptide-derived inhibitors of dipeptidyl peptidases 8 and 9: the impact of P1-variation
    MedChemComm7, 433-438. DOI  I
  13. Waumans,Y., Vliegen,G., Maes,L., Rombouts,M., Declerck,K., Van der Veken,P., Vanden Berghe,W., De Meyer,G.R., Schrijvers,D. and De Meester,I.
    The dipeptidyl peptidases 4, 8, and 9 in mouse monocytes and macrophages: dpp8/9 inhibition attenuates M1 macrophage activation in mice
    Inflammation39, 413-424. PubMed  Europe PubMed DOI
    14. 2015
  14. Huan,Y., Jiang,Q., Liu,J.-L. and Shen,Z.-F.
    Establishment of a dipeptidyl peptidases (DPP) 8/9 expressing cell model for evaluating the selectivity of DPP4 inhibitors
    J Pharmacol Toxicol Methods71, 8-12. PubMed  Europe PubMed DOI  I
    15. 2014
  15. Kwan,J.C., Liu,Y., Ratnayake,R., Hatano,R., Kuribara,A., Morimoto,C., Ohnuma,K., Paul,V.J., Ye,T. and Luesch,H.
    Grassypeptolides as natural inhibitors of dipeptidyl peptidase 8 and T-cell activation
    Chembiochem15, 799-804. PubMed  Europe PubMed DOI  I
    16. 2013
  16. Pilla,E., Kilisch,M., Lenz,C., Urlaub,H. and Geiss-Friedlander,R.
    The SUMO1-E67 interacting loop peptide is an allosteric inhibitor of the dipeptidyl peptidases 8 and 9
    J Biol Chem288, 32787-32796. PubMed  Europe PubMed DOI  I
  17. Wilson,C.H., Indarto,D., Doucet,A., Pogson,L.D., Pitman,M.R., McNicholas,K., Menz,R.I., Overall,C.M. and Abbott,C.A.
    Identifying natural substrates for dipeptidyl peptidases 8 and 9 using terminal amine isotopic labeling of substrates (TAILS) reveals in vivo roles in cellular homeostasis and energy metabolism
    J Biol Chem288, 13936-13949. PubMed  Europe PubMed DOI  P
  18. Zhang,H., Chen,Y., Keane,F.M. and Gorrell,M.D.
    Advances in understanding the expression and function of dipeptidyl peptidase 8 and 9
    Mol Cancer Res11, 1487-1496. PubMed  Europe PubMed DOI
    19. 2012
  19. Abbott,C.A. and Gorrell,M.D.
    Dipeptidyl peptidase 8
    [ISSN:978-0-12-407742-3]3, 3379-3384. DOI
  20. Wu,W., Liu,Y., Milo,L.J., Jr., Shu,Y., Zhao,P., Li,Y., Woznica,I., Yu,G., Sanford,D.G., Zhou,Y., Poplawski,S.E., Connolly,B.A., Sudmeier,J.L., Bachovchin,W.W. and Lai,J.H.
    4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities
    Bioorg Med Chem Lett22, 5536-5540. PubMed  Europe PubMed DOI  I
    21. 2011
  21. Chen,S.J. and Jiaang,W.T.
    Current advances and therapeutic potential of agents targeting dipeptidyl peptidases-IV, -II, 8/9 and fibroblast activation protein
    Curr Top Med Chem11, 1447-1463. PubMed  Europe PubMed DOI  I
  22. Matheeussen,V., Baerts,L., De Meyer,G., De Keulenaer,G., Van der Veken,P., Augustyns,K., Dubois,V., Scharpe,S. and De Meester,I.
    Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries
    Biol Chem392, 189-198. PubMed  Europe PubMed DOI
  23. Van Goethem,S., Matheeussen,V., Joossens,J., Lambeir,A.M., Chen,X., De Meester,I., Haemers,A., Augustyns,K. and Van der Veken,P.
    Structure-activity relationship studies on isoindoline inhibitors of dipeptidyl peptidases 8 and 9 (DPP8, DPP9): is DPP8-selectivity an attainable goal?
    J Med Chem54, 5737-5746. PubMed  Europe PubMed DOI  I
    24. 2010
  24. Kirby,M., Yu,D.M., O'Connor,S. and Gorrell,M.D.
    Inhibitor selectivity in the clinical application of dipeptidyl peptidase-4 inhibition
    Clin Sci (Lond)118, 31-41. PubMed  Europe PubMed DOI  I
  25. Pitman,M.R., Menz,R.I. and Abbott,C.A.
    Hydrophilic residues surrounding the S1 and S2 pockets contribute to dimerisation and catalysis in human dipeptidyl peptidase 8 (DP8)
    Biol Chem391, 959-972. PubMed  Europe PubMed DOI
    26. 2009
  26. Ansorge,S., Bank,U., Heimburg,A., Helmuth,M., Koch,G., Tadje,J., Lendeckel,U., Wolke,C., Neubert,K., Faust,J., Fuchs,P., Reinhold,D., Thielitz,A. and Tager,M.
    Recent insights into the role of dipeptidyl aminopeptidase IV (DPIV) and aminopeptidase N (APN) families in immune functions
    Clin Chem Lab Med47, 253-261. PubMed  Europe PubMed DOI
  27. Dubois,V., Van Ginneken,C., de Cock,H., Lambeir,A.M., Van der Veken,P., Augustyns,K., Chen,X., Scharpe,S. and De Meester,I.
    Enzyme activity and immunohistochemical localization of dipeptidyl peptidase 8 and 9 in male reproductive tissues
    J Histochem Cytochem57, 531-541. PubMed  Europe PubMed DOI
  28. Pitman,M.R., Sulda,M.L., Kuss,B. and Abbott,C.A.
    Dipeptidyl peptidase 8 and 9 - guilty by association?
    Front Biosci14, 3619-3633. PubMed  Europe PubMed  V
  29. Reinhold,D., Goihl,A., Wrenger,S., Reinhold,A., Kuhlmann,U.C., Faust,J., Neubert,K., Thielitz,A., Brocke,S., Tager,M., Ansorge,S. and Bank,U.
    Role of dipeptidyl peptidase IV (DP IV)-like enzymes in T lymphocyte activation: investigations in DP IV/CD26-knockout mice
    Clin Chem Lab Med47, 268-274. PubMed  Europe PubMed DOI  I
  30. Wu,J.J., Tang,H.K., Yeh,T.K., Chen,C.M., Shy,H.S., Chu,Y.R., Chien,C.H., Tsai,T.Y., Huang,Y.C., Huang,Y.L., Huang,C.H., Tseng,H.Y., Jiaang,W.T., Chao,Y.S. and Chen,X.
    Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor
    Biochem Pharmacol78, 203-210. PubMed  Europe PubMed DOI  I
  31. Yazbeck,R., Howarth,G.S. and Abbott,C.A.
    Dipeptidyl peptidase inhibitors, an emerging drug class for inflammatory disease?
    Trends Pharmacol Sci30, 600-607. PubMed  Europe PubMed DOI  I
  32. Yu,D.M., Ajami,K., Gall,M.G., Park,J., Lee,C.S., Evans,K.A., McLaughlin,E.A., Pitman,M.R., Abbott,C.A., McCaughan,G.W. and Gorrell,M.D.
    The in vivo expression of dipeptidyl peptidases 8 and 9
    J Histochem Cytochem57, 1025-1040. PubMed  Europe PubMed DOI
    33. 2008
  33. Ajami,K., Pitman,M.R., Wilson,C.H., Park,J., Menz,R.I., Starr,A.E., Cox,J.H., Abbott,C.A., Overall,C.M. and Gorrell,M.D.
    Stromal cell-derived factors 1alpha and 1beta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8
    FEBS Lett582, 819-825. PubMed  Europe PubMed DOI  P
  34. Burkey,B.F., Hoffmann,P.K., Hassiepen,U., Trappe,J., Juedes,M. and Foley,J.E.
    Adverse effects of dipeptidyl peptidases 8 and 9 inhibition in rodents revisited
    Diabetes Obes Metab10, 1057-1061. PubMed  Europe PubMed DOI
  35. Dubois,V., Lambeir,A.M., Van der Veken,P., Augustyns,K., Creemers,J., Chen,X., Scharpe,S. and De Meester,I.
    Purification and characterization of dipeptidyl peptidase IV-like enzymes from bovine testes
    Front Biosci13, 3558-3568. PubMed  Europe PubMed DOI
  36. Schade,J., Stephan,M., Schmiedl,A., Wagner,L., Niestroj,A.J., Demuth,H.U., Frerker,N., Klemann,C., Raber,K.A., Pabst,R. and von Horsten,S.
    Regulation of expression and function of dipeptidyl peptidase 4 (DP4), DP8/9, and DP10 in allergic responses of the lung in rats
    J Histochem Cytochem56, 147-155. PubMed  Europe PubMed DOI
  37. Van der Veken,P., De Meester,I., Dubois,V., Soroka,A., Van Goethem,S., Maes,M.B., Brandt,I., Lambeir,A.M., Chen,X., Haemers,A., Scharpe,S. and Augustyns,K.
    Inhibitors of dipeptidyl peptidase 8 and dipeptidyl peptidase 9. Part 1: Identification of dipeptide derived leads
    Bioorg Med Chem Lett18, 4154-4158. PubMed  Europe PubMed DOI  I
  38. Van Goethem,S., Van der Veken,P., Dubois,V., Soroka,A., Lambeir,A.M., Chen,X., Haemers,A., Scharpe,S., De Meester,I. and Augustyns,K.
    Inhibitors of dipeptidyl peptidase 8 and dipeptidyl peptidase 9. Part 2: Isoindoline containing inhibitors
    Bioorg Med Chem Lett18, 4159-4162. PubMed  Europe PubMed DOI  I
    39. 2007
  39. Frerker,N., Wagner,L., Wolf,R., Heiser,U., Hoffmann,T., Rahfeld,J.U., Schade,J., Karl,T., Naim,H.Y., Alfalah,M., Demuth,H.U. and von Horsten,S.
    Neuropeptide Y (NPY) cleaving enzymes: structural and functional homologues of dipeptidyl peptidase 4
    Peptides28, 257-268. PubMed  Europe PubMed DOI
  40. Maes,M.B., Dubois,V., Brandt,I., Lambeir,A.M., Van der Veken,P., Augustyns,K., Cheng,J.D., Chen,X., Scharpe,S. and De Meester,I.
    Dipeptidyl peptidase 8/9-like activity in human leukocytes
    J Leukoc Biol81, 1252-1257. PubMed  Europe PubMed DOI
  41. Rummey,C. and Metz,G.
    Homology models of dipeptidyl peptidases 8 and 9 with a focus on loop predictions near the active site
    Proteins66, 160-171. PubMed  Europe PubMed DOI  S
  42. Thornberry,N.A. and Weber,A.E.
    Discovery of JANUVIA (Sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
    Curr Top Med Chem7, 557-568. PubMed  Europe PubMed DOI  I
  43. Van der Veken,P., Soroka,A., Brandt,I., Chen,Y.S., Maes,M.B., Lambeir,A.M., Chen,X., Haemers,A., Scharpe,S., Augustyns,K. and De Meester,I.
    Irreversible inhibition of dipeptidyl peptidase 8 by dipeptide-derived diaryl phosphonates
    J Med Chem50, 5568-5570. PubMed  Europe PubMed DOI  I
  44. Van der Veken,P., Haemers,A. and Augustyns,K.
    Prolyl peptidases related to dipeptidyl peptidase IV: potential of specific inhibitors in drug discovery
    Curr Top Med Chem7, 621-635. PubMed  Europe PubMed DOI  V
    45. 2006
  45. [YEAR:13-2-2006]Bjelke,J.R., Christensen,J., Nielsen,P.F., Branner,S., Kanstrup,A.B., Wagtmann,N. and Rasmussen,H.B.
    Dipeptidyl peptidases 8 and 9: specificity and molecular characterization compared with dipeptidyl peptidase IV
    Biochem J396, 391-399. PubMed  Europe PubMed DOI  P
  46. Bjelke,J.R., Kanstrup,A.B. and Rasmussen,H.B.
    Selectivity among dipeptidyl peptidases of the S9b family
    Cell Mol Biol Incl Cyto Enzymol52, 3-7. PubMed  Europe PubMed DOI  P
  47. Lee,H.J., Chen,Y.S., Chou,C.Y., Chien,C.H., Lin,C.H., Chang,G.G. and Chen,X.
    Investigation of the dimer interface and substrate specificity of prolyl dipeptidase DPP8
    J Biol Chem281, 38653-38662. PubMed  Europe PubMed DOI
  48. Pitman,M.R., Menz,R.I. and Abbott,C.A.
    Prediction of dipeptidyl peptidase (DP) 8 structure by homology modelling
    Adv Exp Med Biol575, 33-42. PubMed  Europe PubMed DOI
  49. Yu,D.M., Wang,X.M., McCaughan,G.W. and Gorrell,M.D.
    Extraenzymatic functions of the dipeptidyl peptidase IV-related proteins DP8 and DP9 in cell adhesion, migration and apoptosis
    FEBS J273, 2447-2460. PubMed  Europe PubMed DOI
    50. 2005
  50. Jiaang,W.T., Chen,Y.S., Hsu,T., Wu,S.H., Chien,C.H., Chang,C.N., Chang,S.P., Lee,S.J. and Chen,X.
    Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8
    Bioorg Med Chem Lett15, 687-691. PubMed  Europe PubMed DOI  I
  51. Lankas,G.R., Leiting,B., Roy,R.S., Eiermann,G.J., Beconi,M.G., Biftu,T., Chan,C.C., Edmondson,S., Feeney,W.P., He,H., Ippolito,D.E., Kim,D., Lyons,K.A., Ok,H.O., Patel,R.A., Petrov,A.N., Pryor,K.A., Qian,X., Reigle,L., Woods,A., Wu,J.K., Zaller,D., Zhang,X., Zhu,L., Weber,A.E. and Thornberry,N.A.
    Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9
    Diabetes54, 2988-2994. PubMed  Europe PubMed DOI  I
  52. [YEAR:1-7-2005]Lu,I.L., Lee,S.J., Tsu,H., Wu,S.Y., Kao,K.H., Chien,C.H., Chang,Y.Y., Chen,Y.S., Cheng,J.H., Chang,C.N., Chen,T.W., Chang,S.P., Chen,X. and Jiaang,W.T.
    Glutamic acid analogues as potent dipeptidyl peptidase IV and 8 inhibitors
    Bioorg Med Chem Lett15, 3271-3275. PubMed  Europe PubMed DOI  I
  53. Zhu,H., Zhou,Z.M., Lu,L., Xu,M., Wang,H., Li,J.M. and Sha,J.H.
    Expression of a novel dipeptidyl peptidase 8 (DPP8) transcript variant, DPP8-v3, in human testis
    Asian J Androl7, 245-255. PubMed  Europe PubMed DOI  R
    54. 2004
  54. Chen,Y.S., Chien,C.H., Goparaju,C.M., Hsu,J.T., Liang,P.H. and Chen,X.
    Purification and characterization of human prolyl dipeptidase DPP8 in Sf9 insect cells
    Protein Expr Purif35, 142-146. PubMed  Europe PubMed DOI
    55. 2000
  55. Abbott,C.A., Yu,D.M., Woollatt,E., Sutherland,G.R., McCaughan,G.W. and Gorrell,M.D.
    Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8
    Eur J Biochem267, 6140-6150. PubMed  Europe PubMed DOI  E

feedback
Page created 8-September-2023

EMBL-EBI logo

© 2025 EBI
Terms of use