Merops Switch to
Inhibitors

Peptidase

Family Clan SEARCHES BLAST
MEROPS SUBMISSIONS

Other
information

Literature for peptidase C01.072: rhodesain

Summary Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Inhibitors

(References are filtered for relevance to Inhibitor. To remove the filter click here. See explanation.)

    2025
  1. Sheu-Idrees,R., Marques,G.V.L., Santana,P.A.L., Diniz,L.A., Resende,D.M., Odoma,S., Olorunshola,O., Ferreira,R.S., Murta,S.M.F., Maltarollo,V.G. and de Oliveira,R.B.
    Investigation of the activity of 4-aminoquinolines as cysteine protease inhibitors with application in the treatment of Chagas disease
    Mem Inst Oswaldo Cruz (2025) 120, e240161-e240161. PubMed  Europe PubMed DOI  PMC  EPMC  I
    2. 2024
  2. Di Chio,C., Starvaggi,J., Totaro,N., Previti,S., Natale,B., Cosconati,S., Bogacz,M., Schirmeister,T., Legac,J., Rosenthal,P.J., Zappala,M. and Ettari,R.
    Development of Novel Peptidyl Nitriles Targeting Rhodesain and Falcipain-2 for the Treatment of Sleeping Sickness and Malaria
    Int J Mol Sci (2024) 25 PubMed  Europe PubMed DOI  PMC  EPMC  I
  3. Nunes,J.A., Santos-Junior,P.F.D.S., Gomes,M.C., Ferreira,L.A.S., Padilha,E.K.A., Teixeira,T.R., Stanger,E.J., Kaur,Y., Silva,E.B.D., Costa,C.A.C.B., Freitas,J.D., Araujo-Junior,J.X., Mendonca-Junior,F.J.B., Giardini,M.A., Siqueira-Neto,J.L., Caffrey,C.R., Zhan,P., Cardoso,S.H. and Silva-Junior,E.F.D.
    Nanomolar activity of coumarin-3-thiosemicarbazones targeting Trypanosoma cruzi cruzain and the T. brucei cathepsin L-like protease
    Eur J Med Chem (2024) 283, 117109-117109. PubMed  Europe PubMed DOI  I
    4. 2021
  4. Barbosa da Silva,E., Rocha,D.A., Fortes,I.S., Yang,W., Monti,L., Siqueira-Neto,J.L., Caffrey,C.R., McKerrow,J., Andrade,S.F. and Ferreira,R.S.
    Structure-Based Optimization of Quinazolines as Cruzain and TbrCATL Inhibitors
    J Med Chem (2021) 64, 13054-13071. PubMed  Europe PubMed DOI  I
  5. Di Chio,C., Previti,S., De Luca,F., Allegra,A., Zappala,M. and Ettari,R.
    Drug combination studies of PS-1 and quercetin against rhodesain of Trypanosoma brucei rhodesiense
    Nat Prod Res (2021) , 1-5. PubMed  Europe PubMed DOI  I
    6. 2020
  6. Arafet,K., Gonzalez,F.V. and Moliner,V.
    Quantum mechanics/molecular mechanics studies of the mechanism of cysteine proteases inhibition by dipeptidyl nitroalkenes
    Chemistry (2020) 26, 2002-2012. PubMed  Europe PubMed DOI  I
  7. da Costa,C.H.S., Bonatto,V., Dos Santos,A.M., Lameira,J., Leitao,A. and Montanari,C.A.
    Evaluating QM/MM free energy surfaces for ranking cysteine protease covalent inhibitors
    J Chem Inf Model (2020) 60, 880-889. PubMed  Europe PubMed DOI  I
  8. Di Chio,C., Previti,S., Amendola,G., Cosconati,S., Schirmeister,T., Zappala,M. and Ettari,R.
    Development of novel benzodiazepine-based peptidomimetics as inhibitors of rhodesain from Trypanosoma brucei rhodesiense
    ChemMedChem (2020) 15, 995-1001. PubMed  Europe PubMed DOI  I
  9. Ettari,R., Previti,S., Di Chio,C., Maiorana,S., Allegra,A., Schirmeister,T. and Zappala,M.
    Drug synergism: studies of combination of RK-52 and curcumin against rhodesain of Trypanosoma brucei rhodesiense
    ACS Med Chem Lett (2020) 11, 806-810. PubMed  Europe PubMed DOI  PMC  EPMC  I
  10. Klein,P., Johe,P., Wagner,A., Jung,S., Kuhlborn,J., Barthels,F., Tenzer,S., Distler,U., Waigel,W., Engels,B., Hellmich,U.A., Opatz,T. and Schirmeister,T.
    New cysteine protease inhibitors: electrophilic (het)arenes and unexpected prodrug identification for the Trypanosoma protease rhodesain
    Molecules (2020) 25 PubMed  Europe PubMed DOI  I
  11. Klein,P., Barthels,F., Johe,P., Wagner,A., Tenzer,S., Distler,U., Le,T.A., Schmid,P., Engel,V., Engels,B., Hellmich,U.A., Opatz,T. and Schirmeister,T.
    Naphthoquinones as covalent reversible inhibitors of cysteine proteases: studies on inhibition mechanism and kineticsNaphthoquinones as Covalent Reversible Inhibitors of Cysteine Proteases: Studies on Inhibition Mechanism and Kinetics
    Molecules (2020) 25 PubMed  Europe PubMed DOI  I
    12. 2019
  12. Cianni,L., Feldmann,C.W., Gilberg,E., Gutschow,M., Juliano,L., Leitao,A., Bajorath,J. and Montanari,C.A.
    Can cysteine protease cross-class inhibitors achieve selectivity?
    J Med Chem (2019) 62, 10497-10525. PubMed  Europe PubMed DOI  I
  13. Ettari,R., Previti,S., Maiorana,S., Allegra,A., Schirmeister,T., Grasso,S. and Zappala,M.
    Drug combination studies of curcumin and genistein against rhodesain of Trypanosoma brucei rhodesiense
    Nat Prod Res (2019) 33, 3577-3581. PubMed  Europe PubMed DOI  I
  14. Santos,L.H., Waldner,B.J., Fuchs,J.E., Pereira,G.A.N., Liedl,K.R., Caffarena,E.R. and Ferreira,R.S.
    Understanding structure-activity relationships for trypanosomal cysteine protease inhibitors by simulations and free energy calculations
    J Chem Inf Model (2019) 59, 137-148. PubMed  Europe PubMed DOI  I
  15. Steverding,D.
    On the reversible and irreversible inhibition of rhodesain by curcumin
    Molecules (2019) 25 PubMed  Europe PubMed DOI  I
    16. 2018
  16. Giroud,M., Kuhn,B., Saint-Auret,S., Kuratli,C., Martin,R.E., Schuler,F., Diederich,F., Kaiser,M., Brun,R., Schirmeister,T. and Haap,W.
    2 H-1,2,3-Triazole-based dipeptidyl nitriles: potent, selective, and trypanocidal rhodesain inhibitors by structure-based design
    J Med Chem (2018) 61, 3370-3388. PubMed  Europe PubMed DOI  I
  17. Giroud,M., Dietzel,U., Anselm,L., Banner,D., Kuglstatter,A., Benz,J., Blanc,J.B., Gaufreteau,D., Liu,H., Lin,X., Stich,A., Kuhn,B., Schuler,F., Kaiser,M., Brun,R., Schirmeister,T., Kisker,C., Diederich,F. and Haap,W.
    Repurposing a library of human cathepsin L ligands: identification of macrocyclic lactams as potent rhodesain and Trypanosoma brucei inhibitors
    J Med Chem (2018) 61, 3350-3369. PubMed  Europe PubMed DOI  S  I
  18. Rocha,D.A., Silva,E.B., Fortes,I.S., Lopes,M.S., Ferreira,R.S. and Andrade,S.F.
    Synthesis and structure-activity relationship studies of cruzain and rhodesain inhibitors
    Eur J Med Chem (2018) 157, 1426-1459. PubMed  Europe PubMed DOI  I
  19. Royo,S., Schirmeister,T., Kaiser,M., Jung,S., Rodriguez,S., Bautista,J.M. and Gonzalez,F.V.
    Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates
    Bioorg Med Chem (2018) 26, 4624-4634. PubMed  Europe PubMed DOI  I
    20. 2017
  20. Giroud,M., Ivkovic,J., Martignoni,M., Fleuti,M., Trapp,N., Haap,W., Kuglstatter,A., Benz,J., Kuhn,B., Schirmeister,T. and Diederich,F.
    Inhibition of the cysteine protease human cathepsin L by triazine nitriles: amide???heteroarene pi-stacking interactions and chalcogen bonding in the S3 pocket
    ChemMedChem (2017) 12, 257-270. PubMed  Europe PubMed DOI  I
  21. Previti,S., Ettari,R., Cosconati,S., Amendola,G., Chouchene,K., Wagner,A., Hellmich,U.A., Ulrich,K., Krauth-Siegel,R.L., Wich,P.R., Schmid,I., Schirmeister,T., Gut,J., Rosenthal,P.J., Grasso,S. and Zappala,M.
    Development of novel peptide-based Michael acceptors targeting rhodesain and falcipain-2 for the treatment of neglected tropical diseases (NTDs)
    J Med Chem (2017) 60, 6911-6923. PubMed  Europe PubMed DOI  I
  22. Schirmeister,T., Schmitz,J., Jung,S., Schmenger,T., Krauth-Siegel,R.L. and Gutschow,M.
    Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei
    Bioorg Med Chem Lett (2017) 27, 45-50. PubMed  Europe PubMed DOI  I
    23. 2016
  23. Ettari,R., Previti,S., Cosconati,S., Kesselring,J., Schirmeister,T., Grasso,S. and Zappala,M.
    Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors
    J Enzyme Inhib Med Chem (2016) 31, 1184-1191. PubMed  Europe PubMed DOI  I
  24. Ettari,R., Previti,S., Tamborini,L., Cullia,G., Grasso,S. and Zappala,M.
    The inhibition of cysteine proteases rhodesain and TbCatB: a valuable approach to treat human African trypanosomiasis
    Mini Rev Med Chem (2016) 16, 1374-1391. PubMed  Europe PubMed DOI  V  I
  25. Latorre,A., Schirmeister,T., Kesselring,J., Jung,S., Johe,P., Hellmich,U.A., Heilos,A., Engels,B., Krauth-Siegel,R.L., Dirdjaja,N., Bou-Iserte,L., Rodriguez,S. and Gonzalez,F.V.
    Dipeptidyl nitroalkenes as potent reversible inhibitors of cysteine proteases rhodesain and cruzain
    ACS Med Chem Lett (2016) 7, 1073-1076. PubMed  Europe PubMed DOI  PMC  EPMC  I
    26. 2015
  26. Ettari,R., Pinto,A., Previti,S., Tamborini,L., Angelo,I.C., La Pietra,V., Marinelli,L., Novellino,E., Schirmeister,T., Zappala,M., Grasso,S., De Micheli,C. and Conti,P.
    Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation
    Bioorg Med Chem (2015) 23, 7053-7060. PubMed  Europe PubMed DOI  I
  27. Fonseca,N.C., da Cruz,L.F., da Silva Villela,F., do Nascimento Pereira,G.A., de Siqueira-Neto,J.L., Kellar,D., Suzuki,B.M., Ray,D., de Souza,T.B., Alves,R.J., Junior,P.A., Romanha,A.J., Murta,S.M., McKerrow,J.H., Caffrey,C.R., de Oliveira,R.B. and Ferreira,R.S.
    Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1
    Antimicrob Agents Chemother (2015) 59, 2666-2677. PubMed  Europe PubMed DOI  I
  28. McShan,D., Kathman,S., Lowe,B., Xu,Z., Zhan,J., Statsyuk,A. and Ogungbe,I.V.
    Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain
    Bioorg Med Chem Lett (2015) 25, 4509-4512. PubMed  Europe PubMed DOI  I
  29. Royo,S., Rodriguez,S., Schirmeister,T., Kesselring,J., Kaiser,M. and Gonzalez,F.V.
    Dipeptidyl enoates as potent rhodesain inhibitors that display a dual mode of action
    ChemMedChem (2015) 10, 1484-1487. PubMed  Europe PubMed DOI  I
    30. 2014
  30. Ettari,R., Pinto,A., Tamborini,L., Angelo,I.C., Grasso,S., Zappala,M., Capodicasa,N., Yzeiraj,L., Gruber,E., Aminake,M.N., Pradel,G., Schirmeister,T., De Micheli,C. and Conti,P.
    Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antiprotozoal agents
    ChemMedChem (2014) 9, 1817-1825. PubMed  Europe PubMed DOI  I
    31. 2013
  31. Ehmke,V., Winkler,E., Banner,D.W., Haap,W., Schweizer,W.B., Rottmann,M., Kaiser,M., Freymond,C., Schirmeister,T. and Diederich,F.
    Optimization of triazine nitriles as rhodesain inhibitors: structure-activity relationships, bioisosteric imidazopyridine nitriles, and X-ray crystal structure analysis with human cathepsin L
    ChemMedChem (2013) 8, 967-975. PubMed  Europe PubMed DOI  I
  32. Ettari,R., Tamborini,L., Angelo,I.C., Grasso,S., Schirmeister,T., Lo Presti,L., De Micheli,C., Pinto,A. and Conti,P.
    Development of rhodesain inhibitors with a 3-bromoisoxazoline warhead
    ChemMedChem (2013) 8, 2070-2076. PubMed  Europe PubMed DOI  I
  33. Ettari,R., Tamborini,L., Angelo,I.C., Micale,N., Pinto,A., De Micheli,C. and Conti,P.
    Inhibition of rhodesain as a novel therapeutic modality for human African trypanosomiasis
    J Med Chem (2013) 56, 5637-5658. PubMed  Europe PubMed DOI  I
    34. 2012
  34. Ehmke,V., Quinsaat,J.E., Rivera-Fuentes,P., Heindl,C., Freymond,C., Rottmann,M., Brun,R., Schirmeister,T. and Diederich,F.
    Tuning and predicting biological affinity: aryl nitriles as cysteine protease inhibitors
    Org Biomol Chem (2012) 10, 5764-5768. PubMed  Europe PubMed DOI  I
  35. Steverding,D., Sexton,D.W., Wang,X., Gehrke,S.S., Wagner,G.K. and Caffrey,C.R.
    Trypanosoma brucei: chemical evidence that cathepsin L is essential for survival and a relevant drug target
    Int J Parasitol (2012) 42, 481-488. PubMed  Europe PubMed DOI  I
  36. Yang,P.Y., Wang,M., Li,L., Wu,H., He,C.Y. and Yao,S.Q.
    Design, synthesis and biological evaluation of potent azadipeptide nitrile inhibitors and activity-based probes as promising anti-Trypanosoma brucei agents
    Chemistry (2012) 18, 6528-6541. PubMed  Europe PubMed DOI  I
    37. 2011
  37. Ehmke,V., Heindl,C., Rottmann,M., Freymond,C., Schweizer,W.B., Brun,R., Stich,A., Schirmeister,T. and Diederich,F.
    Potent and selective inhibition of cysteine proteases from Plasmodium falciparum and Trypanosoma brucei
    ChemMedChem (2011) 6, 273-278. PubMed  Europe PubMed DOI  I
    38. 2010
  38. Breuning,A., Degel,B., Schulz,F., Buchold,C., Stempka,M., Machon,U., Heppner,S., Gelhaus,C., Leippe,M., Leyh,M., Kisker,C., Rath,J., Stich,A., Gut,J., Rosenthal,P.J., Schmuck,C. and Schirmeister,T.
    Michael acceptor based antiplasmodial and antitrypanosomal cysteine protease inhibitors with unusual amino acids
    J Med Chem (2010) 53, 1951-1963. PubMed  Europe PubMed DOI  I
  39. Ettari,R., Zappala,M., Micale,N., Schirmeister,T., Gelhaus,C., Leippe,M., Evers,A. and Grasso,S.
    Synthesis of novel peptidomimetics as inhibitors of protozoan cysteine proteases falcipain-2 and rhodesain
    Eur J Med Chem (2010) 45, 3228-3233. PubMed  Europe PubMed DOI  I
  40. Mott,B.T., Ferreira,R.S., Simeonov,A., Jadhav,A., Ang,K.K., Leister,W., Shen,M., Silveira,J.T., Doyle,P.S., Arkin,M.R., McKerrow,J.H., Inglese,J., Austin,C.P., Thomas,C.J., Shoichet,B.K. and Maloney,D.J.
    Identification and optimization of inhibitors of trypanosomal cysteine proteases: cruzain, rhodesain, and TbCatB
    J Med Chem (2010) 53, 52-60. PubMed  Europe PubMed DOI  S  I
  41. Waag,T., Gelhaus,C., Rath,J., Stich,A., Leippe,M. and Schirmeister,T.
    Allicin and derivates are cysteine protease inhibitors with antiparasitic activity
    Bioorg Med Chem Lett (2010) 20, 5541-5543. PubMed  Europe PubMed DOI  I
    42. 2009
  42. Caffrey,C.R. and Steverding,D.
    Kinetoplastid papain-like cysteine peptidases
    Mol Biochem Parasitol (2009) 167, 12-19. PubMed  Europe PubMed DOI  I
  43. Kerr,I.D., Lee,J.H., Farady,C.J., Marion,R., Rickert,M., Sajid,M., Pandey,K.C., Caffrey,C.R., Legac,J., Hansell,E., McKerrow,J.H., Craik,C.S., Rosenthal,P.J. and Brinen,L.S.
    Vinyl sulfones as antiparasitic agents and a structural basis for drug design
    J Biol Chem (2009) 284, 25697-25703. PubMed  Europe PubMed DOI  PMC  EPMC  S  I
    44. 2008
  44. Jaishankar,P., Hansell,E., Zhao,D.M., Doyle,P.S., McKerrow,J.H. and Renslo,A.R.
    Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomes
    Bioorg Med Chem Lett (2008) 18, 624-628. PubMed  Europe PubMed DOI  I
  45. Mallari,J.P., Shelat,A., Kosinski,A., Caffrey,C.R., Connelly,M., Zhu,F., McKerrow,J.H. and Guy,R.K.
    Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB
    Bioorg Med Chem Lett (2008) 18, 2883-2885. PubMed  Europe PubMed DOI  PMC  EPMC  I
    46. 2007
  46. Gonzalez,F.V., Izquierdo,J., Rodriguez,S., McKerrow,J.H. and Hansell,E.
    Dipeptidyl-alpha,beta-epoxyesters as potent irreversible inhibitors of the cysteine proteases cruzain and rhodesain
    Bioorg Med Chem Lett (2007) 17, 6697-6700. PubMed  Europe PubMed DOI  I
    47. 2006
  47. [YEAR:2-10-2006]Nikolskaia,O.V., de,A.L., Kim,Y.V., Lonsdale-Eccles,J.D., Fukuma,T., Scharfstein,J. and Grab,D.J.
    Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease
    J Clin Invest (2-10-2006) 116, 2739-2747. PubMed  Europe PubMed DOI  I
  48. [YEAR:1-3-2006]Vicik,R., Hoerr,V., Glaser,M., Schultheis,M., Hansell,E., McKerrow,J.H., Holzgrabe,U., Caffrey,C.R., Ponte-Sucre,A., Moll,H., Stich,A. and Schirmeister,T.
    Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents
    Bioorg Med Chem Lett (1-3-2006) 16, 2753-2757. PubMed  Europe PubMed DOI  I
    49. 2005
  49. [YEAR:3-1-2005]Fujii,N., Mallari,J.P., Hansell,E.J., Mackey,Z., Doyle,P., Zhou,Y.M., Gut,J., Rosenthal,P.J., McKerrow,J.H. and Guy,R.K.
    Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain
    Bioorg Med Chem Lett (3-1-2005) 15, 121-123. PubMed  Europe PubMed DOI  I
    50. 2003
  50. [YEAR:20-10-2003]Chiyanzu,I., Hansell,E., Gut,J., Rosenthal,P.J., McKerrow,J.H. and Chibale,K.
    Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain
    Bioorg Med Chem Lett (20-10-2003) 13, 3527-3530. PubMed  Europe PubMed DOI  I
    51. 1999
  51. Scory,S., Caffrey,C.R., Stierhof,Y.D., Ruppel,A. and Steverding,D.
    Trypanosoma brucei: killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Z-Phe-Ala-CHN2
    Exp Parasitol (1999) 91, 327-333. PubMed  Europe PubMed DOI  I
  52. Troeberg,L., Morty,R.E., Pike,R.N., Lonsdale-Eccles,J.D., Palmer,J.T., McKerrow,J.H. and Coetzer,T.H.
    Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei
    Exp Parasitol (1999) 91, 349-355. PubMed  Europe PubMed DOI  I

feedback
Page created 8-September-2023

EMBL-EBI logo

© 2026 EBI
Terms of use