chymotrypsin-like

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.

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.

Proteasome inhibitor IX (PS-IX) is an inhibitor of chymotrypsin-like activity of the 20S proteasome (IC50 ~1 μM). Proteasome inhibitor IX shows potent anticancer activity. Proteasome inhibitor IX exhibits HCT116 p53+ + cells growth inhibitory activity(IC50 = 1.49 μM).

MLN2238 suppresses the chymotrypsin-like proteolytic (β5) site of the 20S proteasome(Ki50=0.93 nM, IC50=3.4 nM ). The biologically active form of MLN9708 (Ixazomib Citrate) is MLN2238 in aqueous solutions or plasma.

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.

PI-1840(IC50 = 27 nM)is a reversible and selective chymotrypsin-like (CT-L) inhibitor, with little proteasome proteolytic effects on trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L).

VR23 is a potent proteasome inhibitor. Data shows IC50 =1 nM for trypsin-like proteasomes, IC50=50-100 nM for chymotrypsin-like proteasomes, and IC50=3 μM for caspase-like proteasomes.

Aclacinomycin A hydrochloride (Aclarubicin HCl) is an anthracycline antibiotic and inhibitor of topoisomerase I II, interfering with DNA transcription and replication, inhibiting tumour invasion and angiogenesis, generating reactive oxygen species (ROS), and inhibiting the catalytic centre of the 20S proteasome. It is indicated for the treatment of relapsed leukaemia and advanced malignant lymphoma.

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).

MG-115 (Z-LL-Nva-CHO) is a potent and reversible inhibitor of proteasome , with K i s of 21 nM and 35 nM for 20S and 26S proteasome, respectively. MG-115 specifically inhibit the chymotrypsin-like activity of the proteasome, induces p53-dependent apoptosis [1] [2] [3].

SP-Chymostatin B is a potent inhibitor of many proteases, including chymotrypsin, papain, chymotrypsin-like serine proteinases, chymases, and lysosomal cysteine proteinases. It weakly inhibits human leucocyte elastase. It is effective at a final concentra

Tripeptidyl peptidase II (TPPII) is a serine peptidase of the subtilisin-type which removes tripeptides from the free NH2 terminus of oligopeptides. AAF-CMK is an irreversible inhibitor of TPPII commonly used at 10-100 μM. It does not significantly interfere with the chymotrypsin-like activity of the proteasome. AAF-CMK also inhibits bleomycin hydrolase and puromycin-sensitive aminopeptidase when used at 50 μM.

Z-LLL-AMC is a fluorogenic substrate for the chymotrypsin-like activity of the 26S proteasome or 20S proteolytic core. Chymotrypsin-like activity can be quantified by fluorescent detection of free AMC (also known as 7-amino-4-methylcoumarin), which is excited at 340-360 nm and emits at 440-460 nm. Z-LLL-AMC is typically used in cell lysates after experimental treatment.

GSK3494245 (DDD01305143) is a potent, selective, orally active inhibitor of chymotrypsin-like activity that binds to the proteasome of WTL.donovani (IC50: 0.16 μM), sandwiched between the β4 and β5 subunits, exhibiting good biosafety properties and suitability for inhibiting chymotrypsin-like activity of the human proteasome (IC50: 26S=13 μM; enriched THP-1 extract IC50=40 μM).

3CPLro-IN-1 (compound A17) is a potent, orally active inhibitor of SARS-CoV-2 3-Chymotrypsin-like cysteine protease (3CLpro) with an IC50 of 5.65 μM, making it an attractive drug target against COVID-19 and also considered an antitumor agent-51.

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.

3CPLro-IN-2 is a potent, orally active inhibitor of SARS-CoV-2 3CLpro (IC50: 1.55 μM, Ki: 6.09 μM). 3-Chymotrypsin-like cysteine protease (3CLpro) is an essential protein for viral replication and is a potential drug target against COVID-19.

CEP-18770 is an orally bioavailable synthetic P2 threonine boronic acid inhibitor of the chymotrypsin-like activity of the proteasome, with potential antineoplastic activity. Proteasome inhibitor CEP 18770 represses the proteasomal degradation of a variety of proteins, including inhibitory kappaBalpha (IkappaBalpha), resulting in the cytoplasmic sequestration of the transcription factor NF-kappaB; inhibition of NF-kappaB nuclear translocation and transcriptional up-regulation of a variety of cell growth-promoting factors; and apoptotic cell death in susceptible tumor cell populations. In vitro studies indicate that this agent exhibits a favorable cytotoxicity profile toward normal human epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells relative to the proteasome inhibitor bortezomib. The intracellular protein IkappaBalpha functions as a primary inhibitor of the proinflammatory transcription factor NF-kappaB.

ONX-0914 (PR-957) TFA is a selective, noncompetitive, irreversible inhibitor of the chymotrypsin-like subunit (LMP7) of the immunoproteasome, effectively blocking cytokine production and mitigating experimental arthritis progression. With a K_i value of 5.2 μM against the mycobacterial proteasome, ONX-0914 TFA also reactivates latent HIV-1 by inducing p-TEFb activation through HSF-1 mediation [1] [2] [3].

Enzyme-IN-1 (compound 1), a peptide-based inhibitor of N-terminal nucleophile (Ntn) hydrolases, specifically targets and inhibits the chymotrypsin-like activity (CT-L) of the 20S proteasome. This compound may possess potential anti-inflammatory properties [1].

Proteasome-activating peptide 1 TFA is a potent activator of the proteasome, enhancing chymotrypsin-like proteasomal catalytic activity and increasing proteolytic rates both in vitro and in culture. It also inhibits protein aggregation in cellular models of amyotrophic lateral sclerosis (ALS) [1].

Z-LLF-CHO (Z-Leu-Leu-Phe-CHO) effectively inhibits the chymotrypsin-like activity of the pituitary multicatalytic proteinase complex with a Ki value of 460 nM and also serves as an inhibitor of NF-κB nuclear translocation, as documented in references [1] [2].

Z-Leu-Leu-Tyr-COCHO is a potent inhibitor of chymotrypsin-like activity, with a Ki value of 3.0 nM [1].

Z-Gly-Pro-Phe-Leu-CHO (Z-GPFL-CHO) is a tetrapeptide aldehyde that acts as a selective and potent proteasome inhibitor, with inhibition constants (Ki) of 1.5 µM for branched-chain amino acid-preferred, 2.3 µM for small neutral amino acid-preferred, and 40.5 µM for chymotrypsin-like activities, and an inhibitory concentration (IC50) of 3.1 µM for peptidyl-glutamyl peptide hydrolyzing activity [1].