Cathepsin Inhibitor

S130 is a high affinity, selective inhibitor of ATG4B (a major cysteine protease) with an IC₅₀ of 3.24 µM. S130 suppresses autophagy flux.

Z-Phe-Ala-diazomethylketone binds directly to Aβ42 monomers and small oligomers. Z-Phe-Ala-diazomethylketone inhibits the formation of Aβ42 dodecamers and inhibits Aβ42 fibril formation in the solution. Z-Phe-Ala-diazomethylketone has the potential for neurodegenerative disorders research.

VBY-825 is an orally available novel reversible cathepsin inhibitor that has high inhibitory potency against cathepsin B, L, S and V, and possesses anti-tumor, anti-inflammatory and analgesic effects.

Asperphenamate, a fungal metabolite of Aspergillus flatiipes with anti-cancer effect, exhibits IC₅₀ values of 92.3 μM, 96.5 μM and 97.9 μM in T47D, MDA-MB-231 and HL-60 cells, respectively.

E 64c is a derivative of naturally occurring epoxide inhibitor of cysteine proteases, a Calcium-activated neutral protease (CANP) inhibitor and a very weak irreversible cathepsin C inhibitor. E 64c exhibits entry-blocking effect for MERS-CoV.

CatD-IN-1 (Compound 5) is a Cathepsin D inhibitor with an IC₅₀ of 0.44 μM. CatD-IN-1 holds potential for research in the field of osteoarthritis .

GB111-NH2 hydrochloride is a cysteine cathepsin inhibitor, and can be used for cancer study.

4-Methylesculetin is an orally active coumarin derivative, with potent anti-oxidant and anti-inflammatory activities. 4-Methylesculetin inhibits myeloperoxidase activity. 4-Methylesculetin protects bone resorption by reducing the elevated levels of bone-joint exoglycosidases, cathepsin-D and tartrate resistant acid phosphatases. 4-Methylesculetin ameliorats the upregulated non-enzymatic inflammatory markers like TNF-α, IL-1β, IL-6, COX-2 and PGE2, which is promising for research of inflammatory diseases.

3-Epiursolic Acid is a triterpenoid that can be isolated from Eriobotrya japonica, acts as a competitive inhibitor of cathepsin L (IC₅₀, 6.5 μM; K_i, 19.5 μM), with no obvious effect on cathepsin B.

GSK-2793660 is an orally active and irreversible inhibitor of Cathepsin C (CTSC). GSK-2793660 can be used for the research of bronchiectasis.

Gardenin B is a methoxyflavone compound and an inhibitor of USP7, ODC (IC₅₀: 6.24 μg/mL), and Cathepsin D (IC₅₀: 5.61 μg/mL). Gardenin B exhibits antioxidant and antitumor activities. Gardenin B shows IC₅₀ values of 8.87 and 10.59 μg/mL for DPPH and NO scavenging, respectively, and also possesses ferric ion reducing ability. Additionally, Gardenin B can inhibit tumor cell proliferation, induce cell cycle arrest and apoptosis. Gardenin B can be used in cancer research.

2-Cyanopyrimidine is a potent and non-selective cysteine protease cathepsin K inhibitor with an IC₅₀ of 170 nM. 2-Cyanopyrimidine is used for osteoporos.

AEP-IN-2 is an asparagine endopeptidase (AEP) inhibitor via block AEP cleavage of APP and Tau. AEP-IN-2 has oral activity and decreases Aβ40 and Aβ42 and p-Tau levels .

Z-FG-NHO-BzOME is a cysteine protease inhibitor that selectively inhibits cathepsin B, cathepsin L, cathepsin S, and papain.

Leupeptin Ac-LL hydrochloride is a broad-spectrum protease inhibitor. Leupeptin Ac-LL hydrochloride inhibits serine, cysteine and threonine proteases, and regulates autophagy. Leupeptin Ac-LL hydrochloride reduces the expression levels of LC3B, iNOS, Cox-2, Beclin-1 and the level of endopeptidases; increases the levels of p62, Arg 1, Msr 1 and Mrc⁻1; and blocks the upregulation of p-PTEN, p-NF-κB, p-PI3K, p-Akt, p-p38 and ERK1/2. Leupeptin Ac-LL hydrochloride inhibits NO, ROS, proinflammatory cytokines, the IFN-γ/IL-10 ratio, phagolysosome fusion, mammalian lysosomal hydrolase activity and SARS-CoV-2 replication; and reverses impaired autophagic flux. Leupeptin Ac-LL hydrochloride is applicable to research related to chronic inflammatory diseases, edema, skin tumorigenesis, COVID-19 and respiratory infections.

Cathepsin Inhibitor 2 is a potent Cathepsin S inhibitor extracted from patent WO2009123623A1, has a K_i of <20 nM.

Y1693 is an orally active RANKL inhibitor with a K_d of 5.03 μM for hRANKL. Y1693 inhibits the activation of the downstream c-fos/NFATc1 signaling pathway by blocking its interaction with RANK. Y1693 significantly inhibits RANKL-induced osteoclast differentiation, F-actin ring formation and bone resorptive activity, while downregulating the mRNA and protein expressions of TRAP, cathepsin K, c-fos and NFATc1. Y1693 shows no obvious cytotoxicity to bone marrow-derived macrophages and osteoclast precursor cells, and exhibits favorable ADME properties. Y1693 improves ovariectomy-induced osteoporosis in mice and reverses ligation-induced periodontal alveolar bone loss. Y1693 is applicable to research related to osteoporosis and periodontal diseases.

Cathepsin L/S-IN-1 is a dual inhibitor of Cathepsin L and Cathepsin S with IC₅₀s of 4.10 μM and 1.79 μM, respectively. Cathepsin L/S-IN-1 shows a significant antimetastatic and invasive effects on pancreatic cancer BxPC-3 and PANC-1 cells.

Atg4B-IN-2 is a potent competitive Atg4B inhibitor with K_i value of 3.1 μM, also possesses declining PLA₂ inhibitory potency, IC₅₀s of 11 μM and 3.5 μM for Atg4B and PLA₂, respectively. Atg4B-IN-2 enhances the anticancer activity of anti-castration-resistant prostate cancer agents via autophagy inhibition.

ONO-5334 is a potent, selective and orally active cathepsin K inhibitor with K_i values of 0.10 nM, 0.049 nM and 0.85 nM for human, rabbit and rat cathepsin K, respectively. ONO 5334 is an effective antiviral compound against SAR-COV-2 virus activity with an EC₅₀ value of 500 nM. ONO-5334 has the potential for the study of osteoporosis and COVID-19 disease.