| S7393 |
Aloxistatin (E64d)
|
Aloxistatin (E64d) is an irreversible and membrane-permeable cysteine protease inhibitor with blood platelet aggregation inhibiting activity. This compound reduced cellular entry of SARS-CoV-2 pseudovirions by 92.3%, as the cysteine protease cathepsin L is required for SARS-CoV-2 viral entry.
|
-
Nat Chem Biol, 2025, 10.1038/s41589-025-01907-2
-
J Exp Clin Cancer Res, 2025, 44(1):317
-
Cell Rep, 2025, 44(4):115507
|
|
| S7396 |
Calpeptin
|
Calpeptin is a potent, cell-permeable calpain inhibitor with ID50 of 52 nM, 34 nM, 138 nM, and 40 nM for Calpain I (porcine erythrocytes), Calpain II (porcine kidney), Papainb, and Calpain I (human platelets), respectively. This compound attenuates apoptosis and intracellular inflammatory changes in muscle cells.
|
-
EMBO Mol Med, 2025, 17(12):3355-3376
-
Transl Psychiatry, 2025, 15(1):52
-
Mol Med, 2025, 31(1):166
|
|
| S1115 |
Odanacatib
|
Odanacatib is a potent, selective, and neutral inhibitor of cathepsin K (human/rabbit) with IC50 of 0.2 nM/1 nM, and demonstrated high selectivity versus off-target cathepsin B, L, S. Phase 3.
|
-
PLoS One, 2025, 20(7):e0327246
-
PLoS One, 2025, 20(7):e0327246
-
Int Dent J, 2025, 75(4):100810
|
|
| S7386 |
MG-101 (ALLN)
|
MG-101 (ALLN, Calpain inhibitor-1, Ac-LLnL-CHO) is a cell-permeable and potent inhibitor of cysteine proteases including calpains and lysosomal cathepsins.
|
-
Cell Biosci, 2024, 14(1):115
-
Exp Hematol Oncol, 2023, 12(1):77
-
Exp Hematol Oncol, 2023, 12(1):77
|
|
| S7379 |
E-64
|
E-64 is an irreversible and selective cysteine protease inhibitor, and also inhibits papain, calpain, and cathepsins B and H, but not serine proteases or aspartic proteases. The IC50 for papain is 9 nM. This compound induces oxidative stress and apoptosis in Filarial Parasite.
|
-
Nat Commun, 2025, 16(1):5403
-
Elife, 2025, 14RP104057
-
bioRxiv, 2024, 2024.09.30.615241
|
|
| S7391 |
Z-FA-FMK
|
Z-FA-FMK ((1S)-Z-FA-FMK) is an irreversible cysteine protease inhibitor, and also inhibits effector caspases.
|
-
Eur J Med Chem, 2025, 300:118108
-
Cancer Res, 2022, can.21.4222
-
Comput Struct Biotechnol J, 2022, 20:2442-2454
|
|
| S3692 |
N-Ethylmaleimide (NEM)
|
NEM (N-Ethylmaleimide) is an organic compound that is derived from maleic acid. It is an irreversible inhibitor of all cysteine peptidases, with alkylation occurring at the active site thiol group. N-Ethylmaleimide (NEM) inactivates endogenous deubiquitinating enzymes (DUBs). N-Ethylmaleimide (NEM) specifically inhibits phosphate transport in mitochondria.
|
-
Inflammation, 2025, 10.1007/s10753-025-02273-w
-
Toxicol Lett, 2025, 406:31-37
-
J Exp Clin Cancer Res, 2024, 43(1):330
|
|
| S2847 |
Cathepsin Inhibitor 1
|
Cathepsin Inhibitor 1 is an inhibitor of Cathepsin (L, L2, S, K, B) with pIC50 of 7.9, 6.7, 6.0, 5.5 and 5.2, respectively.
|
-
bioRxiv, 2025, 2025.09.08.674976
-
Cell Mol Life Sci, 2024, 81(1):442
-
Elife, 2023, 12e79144
|
|
| S7424 |
PD 151746
|
PD 151746 is a selective, cell-permeable calpain inhibitor with Ki of 0.26 μM for μ-Calpain, about 20-fold selectivity over m-calpain.
|
-
PLoS Pathog, 2021, 17(9):e1009889
-
Cell, 2019, 177(5):1262-1279
-
Life Sci, 2019, 222:195-202
|
|
| S7392 |
Loxistatin Acid (E-64C)
|
Loxistatin Acid (E-64C, NSC 694279, EP 475), a derivative of E-64, is an irreversible and membrane-permeant cysteine protease inhibitor. This compound inhibits cathepsin L, a cysteine protease required for SARS-CoV-2 viral entry.
|
-
Nat Chem Biol, 2025, 10.1038/s41589-025-01907-2
-
ACS Chem Biol, 2021, 16(9):1628-1643
-
Sci Signal, 2018, 11(518)eaao0422
|
|
| S0722 |
Cruzain-IN-1
|
Cruzain-IN-1 is a selective inhibitor of trypanosomal cysteine proteases and a covalent and reversible Cruzain inhibitor with IC50 of 10 nM.
|
|
|
| S7395New |
PD 150606
|
PD150606 is a potent and selective inhibitor of calpainwith Ki values of 0.21 µM for µ-calpain and 0.37 µM for m-calpain. It exhibits neuroprotective effects by reducing hypoxic/hypoglycemic injury in cerebrocortical neurons and excitotoxic damage in cerebellar Purkinje cells.
|
-
Exp Eye Res, 2025, 258:110435
|
|
| E2886 |
LY3000328
|
LY 3000328 (Z-FL-COCHO, Compound 5) is a potent and selective Cathepsin S (Cat S) inhibitor with IC50s of 7.7 and 1.67 nM for human Cat S and mouse Cat S, respectively.
|
-
Exp Cell Res, 2025, 450(2):114663
-
Respir Res, 2024, 25(1):441
|
|
| E2899 |
MG132 SSS
|
MG132 SSS(Z-Leu-Leu-Leu-al, MG132) is a potent proteasome and calpain inhibitor with IC50 of 100 nM and 1.2 μM, respectively.
|
-
J Adv Res, 2025, S2090-1232(25)00940-3
|
|
| S0194 |
Balicatib
|
Balicatib (AAE-581) is a potent and selective inhibitor of the osteoclastic enzyme cathepsin K.
|
|
|
| S5611 |
2-cyano-Pyrimidine
|
2-cyano-Pyrimidine is a cathepsin K inhibitor with an IC50 of 170 nM.
|
|
|
| E4453 |
Cathepsin G Inhibitor I
|
Cathepsin G Inhibitor I exhibits reversible, competitive cathepsin G inhibition with IC50 and Ki values of 53 nM and 63 nM respectively. It can be used in antigen-processing studies and for modulation of T cell response in situ and in vivo.
|
|
|
| S1013 |
Bortezomib
|
Bortezomib is a potent 20S proteasome inhibitor with Ki of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. This compound inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors.
|
-
J Proteomics, 2026, 322:105536
-
Signal Transduct Target Ther, 2025, 10(1):81
-
Cell Host Microbe, 2025, 33(4):512-528.e7
|
|
| S3012 |
Pazopanib
|
Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms/CSF1R with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively. This compound induces cathepsin B activation and autophagy.
|
-
Nucleic Acids Res, 2025, 53(4)gkaf107
-
Commun Biol, 2025, 8(1):1185
-
Sci Rep, 2025, 15(1):35889
|
|
| S7380 |
Leupeptin Hemisulfate
|
Leupeptin Hemisulfate is a reversible inhibitor of serine and cysteine proteases. It inhibits cathepsin B (Ki = 6 nM), calpain (Ki = 10 nM), trypsin (Ki = 35 nM), plasmin (Ki = 3.4 μM), and kallikrein (Ki = 19 μM), and has no effect against chymotrypsin, elastase, renin, or pepsin.
|
-
Adv Mater, 2025, e18445.
-
Nat Commun, 2025, 16(1):4069
-
J Adv Res, 2025, S2090-1232(25)00056-6
|
|
| S7420 |
CA-074 methyl ester (CA-074 Me)
|
CA-074 methyl ester (CA-074 Me, Cathepsin B Inhibitor IV) is a membrane-permeable derivative of CA-074 and acts as an irreversible cathepsin B inhibitor.
|
-
Mol Cancer, 2025, 24(1):253
-
Cell Stem Cell, 2025, S1934-5909(25)00330-3
-
NPJ Vaccines, 2025, 10(1):184
|
|
| S7381 |
Pepstatin A
|
Pepstatin A (Pepstatin) is a potent aspartic protease inhibitor, and also inhibits HIV replication. This compound is also an inhibitor of cathepsins D and cathepsins E. It inhibits autophagy by suppressing lysosomal proteases.
|
-
Nat Commun, 2025, 16(1):4069
-
Autophagy, 2025, 21(11):2473-2496
-
J Exp Clin Cancer Res, 2025, 44(1):317
|
|
| S3025 |
PMSF
|
PMSF (Phenylmethylsulfonyl Fluoride, Benzylsulfonyl fluoride) is an irreversible serine/cysteine protease inhibitor.
|
-
Cell Death Discov, 2024, 10(1):171
-
Cell Biosci, 2023, 13(1):9
-
Cell Biosci, 2023, 13(1):9
|
|
| S7394 |
MDL-28170
|
MDL-28170 (Calpain Inhibitor III) is a potent and selective calpain inhibitor of calpain that penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. This compound is also an inhibitor of γ-secretase.
|
-
Int Immunopharmacol, 2025, 167:115682
-
Phytomedicine, 2024, 125:155250
-
Am J Pathol, 2024, S0002-9440(24)00356-0
|
|
| S4591 |
Nitroxoline
|
Nitroxoline (8-Hydroxy-5-nitroquinoline, 5-nitroquinolin-8-ol, 5-Nitro-8-quinolinol, 5-Nitro-8-hydroxyquinoline) is a urinary antibacterial agent active against susceptible gram-positive and gram-negative organisms commonly found in urinary tract infections. This compound impairs tumor progression in vitro and in vivo by inhibiting cathepsin B activity.
|
-
Transl Psychiatry, 2024, 14(1):166
-
Int J Biol Sci, 2022, 18(13):5207-5220
-
Microorganisms, 2022, 10(7)1421
|
|
| S7393 |
Aloxistatin (E64d)
|
Aloxistatin (E64d) is an irreversible and membrane-permeable cysteine protease inhibitor with blood platelet aggregation inhibiting activity. This compound reduced cellular entry of SARS-CoV-2 pseudovirions by 92.3%, as the cysteine protease cathepsin L is required for SARS-CoV-2 viral entry. |
- Nat Chem Biol, 2025, 10.1038/s41589-025-01907-2
- J Exp Clin Cancer Res, 2025, 44(1):317
- Cell Rep, 2025, 44(4):115507
|
|
| S7396 |
Calpeptin
|
Calpeptin is a potent, cell-permeable calpain inhibitor with ID50 of 52 nM, 34 nM, 138 nM, and 40 nM for Calpain I (porcine erythrocytes), Calpain II (porcine kidney), Papainb, and Calpain I (human platelets), respectively. This compound attenuates apoptosis and intracellular inflammatory changes in muscle cells. |
- EMBO Mol Med, 2025, 17(12):3355-3376
- Transl Psychiatry, 2025, 15(1):52
- Mol Med, 2025, 31(1):166
|
|
| S1115 |
Odanacatib
|
Odanacatib is a potent, selective, and neutral inhibitor of cathepsin K (human/rabbit) with IC50 of 0.2 nM/1 nM, and demonstrated high selectivity versus off-target cathepsin B, L, S. Phase 3. |
- PLoS One, 2025, 20(7):e0327246
- PLoS One, 2025, 20(7):e0327246
- Int Dent J, 2025, 75(4):100810
|
|
| S7386 |
MG-101 (ALLN)
|
MG-101 (ALLN, Calpain inhibitor-1, Ac-LLnL-CHO) is a cell-permeable and potent inhibitor of cysteine proteases including calpains and lysosomal cathepsins. |
- Cell Biosci, 2024, 14(1):115
- Exp Hematol Oncol, 2023, 12(1):77
- Exp Hematol Oncol, 2023, 12(1):77
|
|
| S7379 |
E-64
|
E-64 is an irreversible and selective cysteine protease inhibitor, and also inhibits papain, calpain, and cathepsins B and H, but not serine proteases or aspartic proteases. The IC50 for papain is 9 nM. This compound induces oxidative stress and apoptosis in Filarial Parasite. |
- Nat Commun, 2025, 16(1):5403
- Elife, 2025, 14RP104057
- bioRxiv, 2024, 2024.09.30.615241
|
|
| S7391 |
Z-FA-FMK
|
Z-FA-FMK ((1S)-Z-FA-FMK) is an irreversible cysteine protease inhibitor, and also inhibits effector caspases. |
- Eur J Med Chem, 2025, 300:118108
- Cancer Res, 2022, can.21.4222
- Comput Struct Biotechnol J, 2022, 20:2442-2454
|
|
| S3692 |
N-Ethylmaleimide (NEM)
|
NEM (N-Ethylmaleimide) is an organic compound that is derived from maleic acid. It is an irreversible inhibitor of all cysteine peptidases, with alkylation occurring at the active site thiol group. N-Ethylmaleimide (NEM) inactivates endogenous deubiquitinating enzymes (DUBs). N-Ethylmaleimide (NEM) specifically inhibits phosphate transport in mitochondria. |
- Inflammation, 2025, 10.1007/s10753-025-02273-w
- Toxicol Lett, 2025, 406:31-37
- J Exp Clin Cancer Res, 2024, 43(1):330
|
|
| S2847 |
Cathepsin Inhibitor 1
|
Cathepsin Inhibitor 1 is an inhibitor of Cathepsin (L, L2, S, K, B) with pIC50 of 7.9, 6.7, 6.0, 5.5 and 5.2, respectively. |
- bioRxiv, 2025, 2025.09.08.674976
- Cell Mol Life Sci, 2024, 81(1):442
- Elife, 2023, 12e79144
|
|
| S7424 |
PD 151746
|
PD 151746 is a selective, cell-permeable calpain inhibitor with Ki of 0.26 μM for μ-Calpain, about 20-fold selectivity over m-calpain.
|
- PLoS Pathog, 2021, 17(9):e1009889
- Cell, 2019, 177(5):1262-1279
- Life Sci, 2019, 222:195-202
|
|
| S7392 |
Loxistatin Acid (E-64C)
|
Loxistatin Acid (E-64C, NSC 694279, EP 475), a derivative of E-64, is an irreversible and membrane-permeant cysteine protease inhibitor. This compound inhibits cathepsin L, a cysteine protease required for SARS-CoV-2 viral entry. |
- Nat Chem Biol, 2025, 10.1038/s41589-025-01907-2
- ACS Chem Biol, 2021, 16(9):1628-1643
- Sci Signal, 2018, 11(518)eaao0422
|
|
| S0722 |
Cruzain-IN-1
|
Cruzain-IN-1 is a selective inhibitor of trypanosomal cysteine proteases and a covalent and reversible Cruzain inhibitor with IC50 of 10 nM. |
|
|
| S7395New |
PD 150606
|
PD150606 is a potent and selective inhibitor of calpainwith Ki values of 0.21 µM for µ-calpain and 0.37 µM for m-calpain. It exhibits neuroprotective effects by reducing hypoxic/hypoglycemic injury in cerebrocortical neurons and excitotoxic damage in cerebellar Purkinje cells. |
- Exp Eye Res, 2025, 258:110435
|
|
| E2886 |
LY3000328
|
LY 3000328 (Z-FL-COCHO, Compound 5) is a potent and selective Cathepsin S (Cat S) inhibitor with IC50s of 7.7 and 1.67 nM for human Cat S and mouse Cat S, respectively. |
- Exp Cell Res, 2025, 450(2):114663
- Respir Res, 2024, 25(1):441
|
|
| E2899 |
MG132 SSS
|
MG132 SSS(Z-Leu-Leu-Leu-al, MG132) is a potent proteasome and calpain inhibitor with IC50 of 100 nM and 1.2 μM, respectively. |
- J Adv Res, 2025, S2090-1232(25)00940-3
|
|
| S0194 |
Balicatib
|
Balicatib (AAE-581) is a potent and selective inhibitor of the osteoclastic enzyme cathepsin K. |
|
|
| S5611 |
2-cyano-Pyrimidine
|
2-cyano-Pyrimidine is a cathepsin K inhibitor with an IC50 of 170 nM. |
|
|
| E4453 |
Cathepsin G Inhibitor I
|
Cathepsin G Inhibitor I exhibits reversible, competitive cathepsin G inhibition with IC50 and Ki values of 53 nM and 63 nM respectively. It can be used in antigen-processing studies and for modulation of T cell response in situ and in vivo. |
|
|
| S1013 |
Bortezomib
|
Bortezomib is a potent 20S proteasome inhibitor with Ki of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. This compound inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors. |
- J Proteomics, 2026, 322:105536
- Signal Transduct Target Ther, 2025, 10(1):81
- Cell Host Microbe, 2025, 33(4):512-528.e7
|
|
| S7380 |
Leupeptin Hemisulfate
|
Leupeptin Hemisulfate is a reversible inhibitor of serine and cysteine proteases. It inhibits cathepsin B (Ki = 6 nM), calpain (Ki = 10 nM), trypsin (Ki = 35 nM), plasmin (Ki = 3.4 μM), and kallikrein (Ki = 19 μM), and has no effect against chymotrypsin, elastase, renin, or pepsin. |
- Adv Mater, 2025, e18445.
- Nat Commun, 2025, 16(1):4069
- J Adv Res, 2025, S2090-1232(25)00056-6
|
|
| S7420 |
CA-074 methyl ester (CA-074 Me)
|
CA-074 methyl ester (CA-074 Me, Cathepsin B Inhibitor IV) is a membrane-permeable derivative of CA-074 and acts as an irreversible cathepsin B inhibitor. |
- Mol Cancer, 2025, 24(1):253
- Cell Stem Cell, 2025, S1934-5909(25)00330-3
- NPJ Vaccines, 2025, 10(1):184
|
|
| S7381 |
Pepstatin A
|
Pepstatin A (Pepstatin) is a potent aspartic protease inhibitor, and also inhibits HIV replication. This compound is also an inhibitor of cathepsins D and cathepsins E. It inhibits autophagy by suppressing lysosomal proteases. |
- Nat Commun, 2025, 16(1):4069
- Autophagy, 2025, 21(11):2473-2496
- J Exp Clin Cancer Res, 2025, 44(1):317
|
|
| S3025 |
PMSF
|
PMSF (Phenylmethylsulfonyl Fluoride, Benzylsulfonyl fluoride) is an irreversible serine/cysteine protease inhibitor. |
- Cell Death Discov, 2024, 10(1):171
- Cell Biosci, 2023, 13(1):9
- Cell Biosci, 2023, 13(1):9
|
|
| S7394 |
MDL-28170
|
MDL-28170 (Calpain Inhibitor III) is a potent and selective calpain inhibitor of calpain that penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. This compound is also an inhibitor of γ-secretase. |
- Int Immunopharmacol, 2025, 167:115682
- Phytomedicine, 2024, 125:155250
- Am J Pathol, 2024, S0002-9440(24)00356-0
|
|
| S4591 |
Nitroxoline
|
Nitroxoline (8-Hydroxy-5-nitroquinoline, 5-nitroquinolin-8-ol, 5-Nitro-8-quinolinol, 5-Nitro-8-hydroxyquinoline) is a urinary antibacterial agent active against susceptible gram-positive and gram-negative organisms commonly found in urinary tract infections. This compound impairs tumor progression in vitro and in vivo by inhibiting cathepsin B activity. |
- Transl Psychiatry, 2024, 14(1):166
- Int J Biol Sci, 2022, 18(13):5207-5220
- Microorganisms, 2022, 10(7)1421
|
|