Proteasome

MG-132 (Z-Leu-Leu-Leu-al) is a 26S proteasome inhibitor (IC50=100 nM) that is cell-permeable and reversible. MG-132 acts as an autophagy activator and also induces apoptosis.

Marizomib is a novel irreversible brain-permeable proteasome inhibitor that inhibits CT-L (β5), CT-T-laspase-like (C-L, β1), and trypsin-like (T-L, β2) 20S proteasomes with IC50s of 3.5, 28, and 430 nM.[3]

UK-101 is a potent and selective inhibitor of the immunoproteasome LMP2, inhibiting β1i (LMP2), β1c (LMP2), and β5 (LMP2), with IC50s of 104 nM, 15 μM, and 1 μM, respectively. UK-101 exhibits a 144-fold and 10-fold higher affinity for β1i than for the distribution of β1c and β5 subunits. UK-101 induces apoptosis and can be used to study prostate cancer-related diseases.

Bortezomib (LDP 341) is a 20S proteasome inhibitor (Ki=0.6 nM) that is reversible and selective. Bortezomib has antitumor activity and inhibits NF-κB, which can disrupt the cell cycle and induce apoptosis.

Aprotinin (Traskolan) is a broad-spectrum serine protease (BPTI) inhibitor that inhibits the activity of a number of different esterases and proteases. Aprotinin is an antifibrinolytic agent used to minimize hemorrhage during complex surgical procedures.

Epoxomicin (BU-4061T,Aids010837) is a selective proteasome inhibitor with anti-inflammatory activity, inhibits primarily the CH-L activity of the 20S proteasome, while T-L and PGPH catalytic activities are also inhibited at 100- and 1000-fold reduced rate.

Pepstatin (Pepsin Inhibitor S 735A) is an aspartate protease inhibitor that also inhibits HIV protease activity with specific and oral activity. Pepstatin inhibits autophagy.

Tripterin (Celastrol) is a natural product, a proteasome inhibitor that inhibits the pancreatic rennet-like activity of the 20S proteasome (IC50=2.5 μM). Tripterin has anti-inflammatory, anti-infectious, and immunomodulatory properties.

ONX-0914 (PR-957) is a potent and highly specific immunoproteasome inhibitor with minimal cross-reactivity to the constitutive proteasome.

Talabostat mesylate (PT100) is an orally active, selective inhibitor of dipeptidyl peptidases IV (DPP4, IC50: 0.18 nM), including tumor-associated fibroblast activation protein. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis.

TCH-165 is a small molecule modulator of proteasome assembly, resulting in an increase in 20S levels. The increase in the level of free 20S corresponds to enhanced proteolysis of IDPs.

Puromycin aminonucleoside (NSC-3056) increases podocyte permeability by modulating ZO-1 in an oxidative stress-dependent manner.

Linagliptin (BI 1356) is a potent, orally bioavailable dihydropurinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity.

Tomatine (lycopersicin) is an antiproliferatve agent of breast adenocarcinoma cells.

Saikogenin A is a dipeptidyl peptidase-4 inhibitor.

LXE408 fumarate is an orally active, non-competitive and kinetoplastid-selective proteasome inhibitor. LXE408 fumarate has an IC50 of 0.04 μM for L. donovani proteasome and an EC50 of 0.04 μM for L. donovani. LXE408 fumarate has a low propensity to cross the blood brain barrier. LXE408 fumarate has the potential for visceral leishmaniasis (VL) research.

Brensocatib (AZD7986) is a Dipeptidyl peptidase 1 (DPP1) inhibitor (pIC50s: 6.85, 7.7, 7.6, 7.8, and 7.8 in human, rat, mouse, rabbit, and dog, respectively).

Ixazomib (MLN2238) , a second generation, boron-containing peptide proteasome inhibitor (PI), inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome (IC50 Ki: 3.4 0.93 nM, in cell-free assays), also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites (IC50: 31 3500 nM).

(R)-MG-132 (Z-Leu-D-leu-leu-al) is the enantiomer of MG-132.

Oprozomib (PR-047) (ONX 0912) , an inhibitor for CT-L activity of 20S proteasome β5(IC50=36 nM) LMP7(IC50=82 nM), is orally bioavailable. Oprozomib also has potential antineoplastic activity.

Carfilzomib (PR-171) is a proteasome inhibitor that irreversibly binds to the chymotrypsin of the 20S proteasome. Carfilzomib has antitumor activity and may be used to treat multiple myeloma.

Sitagliptin (MK0431), a new oral hypoglycemic (anti-diabetic drug), is a new dipeptidyl peptidase-4 (DPP-4) inhibitor. This enzyme-inhibiting drug is used either alone or in combination with metformin or thiazolidinedione for treatment of type 2 diabetes mellitus. The drug can competitively inhibit a protein enzyme and DPP-4, that leads to an incremental amount of active incretins (GLP-1 and GIP), the diminished amount of release of glucagon and increased release of insulin.

RA190 inhibits proteasome function by covalently binding to cysteine 88 of ubiquitin receptor RPN13.

K-7174 dihydrochloride is a proteasome and GATA inhibitor that inhibits neuronal degeneration and induces apoptosis.

Gly-Pro-pNA hydrochloride (Gly-Pro p-nitroanilide hydrochloride) is a dipeptidyl peptidase inhibitor that inhibits dipeptidyl peptidase II, dipeptidyl peptidase IV and dipeptidyl peptidase IX.

Alogliptin Benzoate (SYR 322)(SYR 322), an effective and specific DPP-4 inhibitor (IC50<10 nM), exhibits greater than 10, 000-fold selectivity over DPP-8 9. Alogliptin may inhibit inflammatory responses by preventing the toll-like receptor 4 (TLR-4)-mediated formation of proinflammatory cytokines.

1G244 is an inhibitor of DPP8 9 with antiatherosclerotic and antimyeloma properties. 1G244 had the IC50 values of 14 and 53 nM against DPP8 and DPP9, and The Ki values for 1G244 were 0.9 and 4.2 nM for DPP8 and DPP9

Calpeptin is a potent, cell-permeable calpain inhibitor.

Sitagliptin phosphate monohydrate (MK-0431 phosphate monohydrate) is a potent DPP-IV inhibitor with an IC50 of 19 nM in Caco-2 cell extracts.

Omarigliptin is a potent and selective oral dipeptidyl peptidase 4 (DPP4) inhibitor with IC50 value of 1.6 nM. [3]

Cilastatin (MK0791) is a renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, IMIPENEM, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4.

18α-Glycyrrhetinic acid (Enoxolone) is an inhibitor of NF-kB and an activator of the proteasome, and functions as a longevity-promoting and anti-aggregation factor in multicellular organisms. It induces apoptosis.

Delanzomib (CEP-18770) is an orally active inhibitor of the chymotrypsin-like activity of proteasome (IC50: 3.8 nM). It only marginally inhibits the tryptic and peptidylglutamyl activities of the proteosome.

Ixazomib citrate (MLN9708) is a prodrug of Ixazomib (MLN-2238) and an orally bioavailable second-generation proteasome inhibitor with an IC50 of 3.4 nM, exhibiting potential antineoplastic activity.

Teneligliptin hydrobromide (MP-513 (hydrobromide)) is a novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor; competitively inhibited human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50 values of approximately 1 nM.

3-O-Feruloylquinic acid is a protease inhibitor, it exerts moderate inhibitory effect against AIV (H5N1) in vitro.

MG-101 (Calpain inhibitor I) is a cell-permeable and potent inhibitor of cysteine proteases including calpains and lysosomal cathepsins.

20S Proteasome activator 1 is a 20S proteasome activator with IC50 values of 0.3 μM for trypsin-like sites, 0.7 μM for chymotrypsin-like sites, and 1.8 μM for caspase sites. It prevents the accumulation of pathogenic alpha-synuclein (A53T) mutants through translation in the cellular system, thereby reducing the probability of disease occurrence. 20S Proteasome activator 1 can be used to study neurodegenerative diseases.

(1S,2S)-Bortezomib (Bortezomib) is an enantiomer of Bortezomib. Bortezomib is a reversible and selective inhibitor of the proteasome with a Ki of 0.6 nM for 20S proteasome.

Racecadotril (Acetorphan) has been investigated for the basic science and treatment of Diarrhea, Acute Diarrhea, and Acute Gastroenteritis.

Vildagliptin (LAF237) is a cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Vildagliptin's cyano moiety undergoes hydrolysis and this inactive metabolite is excreted mainly via the urine.

N-alpha-Tosyl-L-lysine chloromethyl ketone hydrochloride (N-alpha-Tosyl-L-lysine_chloromethyl_ketone_hydrochloride) is an inhibitor of trypsin-like protease and exhibits an inhibitory effect on IFN-γ activities.

DBPR108 is an orally bioavailable dipeptide-derived DPP4 inhibitor (IC50: 15 nM) and it has no inhibition on DDP8 and DPP9.

Trelagliptin (SYR-472) is a highly specific, long-acting DPP-4 inhibitor.

4'-Hydroxychalcone (2-Benzal-4-Hydroxyacetophenone) is a chalcone metabolite with hepatoprotective activity

ML604440 is a cell permeable proteasome β1i (LMP2) subunit inhibitor.

Alogliptin (SYR-322)(SYR-322) is a potent, selective inhibitor of DPP-4 with IC50 of <10 nM, exhibits greater than 10, 000-fold selectivity over DPP-8 and DPP-9.

MDL-28170 (Calpain Inhibitor III) is a cysteine protease.