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. Author manuscript; available in PMC: 2020 May 1.
Published in final edited form as: Cancer Lett. 2019 Feb 20;449:207–214. doi: 10.1016/j.canlet.2019.02.035

Table 2.

Cathepsin B inhibitors and their appropriate mechanism of action available to inhibit cathepsin B

Inhibitor Chemistry Mechanism Source Reference
Z-Phe-AlaCH2F fluoromethyl ketone 3-(N-benzyloxycarbonylphenylalanylamido)-DL-1-fluoro-2-butanone Irreversible covalent inhibitor synthesized Rasnick D. Synthesis of peptide fluoromethyl ketones and the inhibition of human Cathepsin B. Anal Biochem. 1985 Sep;149(2):461–5.
E-64 C15N5H2705 Irreversible covalent inhibitor Aspergillus japonicus TPR-64 Hanada K, Tamai M, Yamagishi M, Ohmura S, Sawada J, Tanaka I. Isolation and characterization of E-64, a new thiol protease inhibitor. Agric Biol Chem. 1978;42:523–528.
E64d EST, Loxistatin, ethyl (2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylate Irreversible covalent inhibitor synthesized Hashida S, Towatari T, Kominami E, Katunuma N. Inhibitions by E-64 derivatives of rat liver Cathepsin B and Cathepsin L in vitro and in vivo. J Biochem. 1980 Dec;88(6):1805–11.
iodo and diiodotyrosine E-64-c analogs Iodo and diiodotyrosine epoxysuccinyl derivatives Irreversible covalent inhibitor synthesized Giordano C, Calabretta R, Gallina C, Consalvi V, Scandurra R, Noya FC. Iodo and diiodotyrosine epoxysuccinyl derivatives as selective inhibitors of Cathepsin B. Eur J Med Chem. 1993;28:917–926.
CA-074 and its derivates ( CA-074 Me) [L-3-trans-(propylcarbamoyl)oxirane-2- carbonyl]-L-isoleucyl-L-proline Irreversible covalent inhibitor synthesized Montaser M, Lalmanach G, Mach L. CA-074, but not its methyl ester CA-074Me, is a selective inhibitor of Cathepsin B within living cells. Biol Chem. 2002 Jul-Aug;383(7–8):1305–8.
Miraziridine A aziridinylpeptide Irreversible covalent inhibitor Theonella mirabilis Theonella swinhoei Nakao Y, Fujita M, Warabi K, Matsunaga S, Fusetani N. Miraziridine A a novel cysteine protease inhibitor from the marine sponge theonella aff. mirabilis. J Am Chem Soc. 2000;122:10462– 10463.
Bz-Phe-Arg-CH2F peptide derivative of arginylfluoromethane Irreversible covalent inhibitor synthesized Angliker H, Wikström P, Rauber P, Stone S, Shaw E. Synthesis and properties of peptidyl derivatives of arginylfluoromethanes. Biochem J. 1988 Dec 1;256(2):481–6.
diazomethyl ketones Benzyloxycarbonyl-phenylalanyl diazomethyl ketone and benzyloxy-carbonyl-phenylalanyl-phenylalanyl diazomethyl ketone Irreversible covalent inhibitor synthesized Leary R, Shaw E. Inactivation of Cathepsin B1 by diazomethyl ketones. Biochem Biophys Res Commun. 1977 Dec 7;79(3):926–31.
peptidyl (acyloxy)methanes peptidyl (acyloxy)methanes Irreversible covalent inhibitor synthesized Krantz A. Peptidyl (acyloxy)methanes as quiescent affinity labels for cysteine proteinases. Methods Enzymol. 1994;244:656–71.
1,2,4-thiadiazole derivate thiadiazoles 3a–h Irreversible covalent inhibitor synthesized Leung-Toung R, Wodzinska J, Li W, Lowrie J, Kukreja R, Desilets D, Karimian K, Tam TF. 1,2,4-thiadiazole: a novel Cathepsin B inhibitor. Bioorg Med Chem. 2003 Dec 1;11(24):5529–37.
Calpain inhibitor II N-Acetyl-Leu-Leu-Methional Reversible inhibitor synthesized Sasaki T, Kishi M, Saito M, Tanaka T, Higuchi N, Kominami E, Katunuma N, Murachi T. Inhibitory effect of di- and tripeptidyl aldehydes on calpains and Cathepsins. J Enzyme Inhib. 1990;3(3):195–201.
Peptidyl cyclopropenone 9 Peptidyl cyclopropenone 9 (the S isomer) Reversible inhibitor synthesized Cohen M, Bretler U, Albeck A. Peptidyl cyclopropenones: reversible inhibitors, irreversible inhibitors, or substrates of cysteine proteases? Protein Sci. 2013 Jun;22(6):788–99.
shRNA-CTSB#2 oligonucleotide RNA interference inhibitor synthesized Bao W, Fan Q, Luo X, Cheng WW, Wang YD, Li ZN, Chen XL, Wu D. Silencing of Cathepsin B suppresses the proliferation and invasion of endometrial cancer. Oncol Rep. 2013 Aug;30(2):723–30.
DARPin 8h6 ankyrin repeat protein antibody-drug conjugate like inhibitor synthesized Kramer L, Renko M, Završnik J, Turk D, Seeger MA, Vasiljeva O, Grütter MG, Turk V, Turk B. Non-invasive in vivo imaging of tumour-associated Cathepsin B by a highly selective inhibitory DARPin. Theranostics. 2017 Jul 8;7(11):2806–21.
Concanamycin A designated folimycin Indirect inhibitor (by specific inhibiton of V-ATPase) synthesized Uhlman A, Folkers K, Liston J, Pancholi H, Hinton A. Effects of Vacuolar H(+)-ATPase Inhibition on Activation of Cathepsin B and Cathepsin L Secreted from MDA-MB231 Breast Cancer Cells. Cancer Microenviron. 2017 Dec;10(1–3):49–56.