proteasome

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).

Proteasome β2c/i-IN-1 (compound 37) serves as a selective inhibitor targeting the β2c and β2i subunits of the human proteasome [1].

Proteasome-IN-5, also known as compound 5, acts as a proteasome inhibitor [1].

Proteasome-activating peptide 1 enhances chymotrypsin-like proteasomal catalytic activity, boosting proteolytic rates both in vitro and within cultured cells. Additionally, it inhibits protein aggregation in a cellular model of amyotrophic lateral sclerosis [1].

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

Proteasome-IN-3 is an inhibitor of proteasome-associated DUBs.

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

Proteasome-IN-4, a non-covalent proteasome inhibitor (IC 50 = 8.39 nM), exhibits potent antiproliferative effects on RPMI-8226, MM-1S, and MV-4-11 cell lines, making it valuable for cancer research.

20S Proteasome-IN-4 (Compound 7) is an orally active inhibitor of the 20S proteasome, selectively targeting the parasite form and demonstrating brain penetration capabilities. It exhibits a potent IC50 value of 6.3 nM against the T. b. brucei 20S proteasome, rendering it applicable for human African trypanosomiasis (HAT) research [1].

Proteasome-IN-1 is an inhibitor of proteasome.

Marizomib (ML858) 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, respectively.

ARV-471 (Vepdegestrant) is a orally active Cereblon -based estrogen receptor (ER) PROTAC degrader. ARV-471 is developed for the research of breast cancer.

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.

1. Sanggenon C (Sanggenone C) inhibits tumor cellular proteasomal activity and cell viability, via induction of cell cycle arrest and cell death , inhibiting the proteasome function. 2. Sanggenon C and O inhibited NO production and iNOS expression by suppressing NF-κB activity and IκBα activation; inhibited TNF-alpha -stimulated PMN-HSC adhesion and expression of VCAM-1 by suppressing the activation of NF-kappaB.

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.

1. ISOGINKGETIN (4',4'''-Dimethylamentoflavone), a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectin production. 2. Isoginkgetin has anti-tumor activity, the mechanistic basis is splicing inhibition , thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents.3. Isoginkgetin can inhibit tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression. 4. Isoginkgetin (0.3mg/kg ip for 3d) can reduce the level of O2·- in plasma and erythroeyte and sometimes increase the activity of SOD in anoxic rats, the action being stronger than aspirin.

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.

Torbafylline, a xanthine derivative, is a phosphodiesterase (PDE) inhibitor that attenuates burn-induced protein hydrolysis in rat skeletal muscle through activation of the PDE4/cAMP/EPAC/PI3K/Akt pathway, and inhibits the enhanced ubiquitin-proteasome-dependent protein hydrolysis in skeletal muscle of cancer- and sepsis-prone rats.

m-PEG9-SH is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.

Cbz-NH-PEG12-C2-acid is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.

USP28-IN-4 is a potent USP28 inhibitor with an IC50 value of 0.04 μM against USP28. USP28-IN-4 exhibits anticancer activity and inhibits USP2, USP7, USP8, USP9x, UCHL3 and UCHL5. USP28-IN-4 is cytotoxic to human colorectal and lung squamous carcinoma cells and dose-dependently downregulates c-Myc cellular levels through the ubiquitin-proteasome system. -proteasome system to dose-dependently downregulate cellular levels of c-Myc.

Bortezomib-pinanediol is a proteasome inhibitor. is a prodrug of Bortezomib.

Arimoclomol (BRX-220 free base) is a co-inducer of heat shock proteins (HSP) and can be used in studies about the treatment of amyotrophic lateral sclerosis (ALS).

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.

USP28-IN-3 is a highly selective USP28 inhibitor with an IC50 value of 0.1 μM against USP28.USP28-IN-3 exhibits anticancer activity and inhibits USP2, USP7, USP8, USP9x, UCHL3, and UCHL5.USP28-IN-3 is cytotoxic to human colorectal and lung squamous carcinoma cells, inhibiting c-cells and c-neutralizing c-neutralizing c-neutralizing c-neutralizing c-neutralizing c-neutralizing c-neutralizing c-cells through the ubiquitin-proteasome system. -proteasome system to dose-dependently downregulate cellular levels of c-Myc.

Capzimin is a selective inhibitor of proteasome isopeptidase Rpn11.

E3 ligase Ligand 23 is a cereblon binding agent that degrades Ikaros or Aiolos via the ubiquitin proteasome.

AOH1996 is an orally active ligand for the replicasome component PCNA (proliferating cell nuclear antigen), targeting the transcription-replication conflict (TRC).AOH1996 interferes with the interaction of PCNA with its binding proteins, leading to DNA replication stress and apoptosis.AOH1996 causes proteasome-dependent rpb1 degradation and lethal DNA damage by stabilizing the interaction between PCNA and RNA polymerase II.AOH1996 acts synergistically with DNA damaging agents to inhibit tumor cell growth. AOH1996 inhibits tumor cell growth by stabilizing the interaction between PCNA and RNA polymerase II, leading to proteasome-dependent rpb1 degradation and lethal DNA damage.AOH1996 acts synergistically with DNA damaging agents.

Immunoproteasome inhibitor 1 is a highly potent and reversible inhibitor of both immunoproteasome and proteasome activity. It exhibits time-independent inhibitory effects on immunoproteasome subunits β5c, β1i, and β5i, with respective Ki values of 1.18 μM, 0.27 μM, and 1.91 μM. This compound shows promising potential for the treatment of select neoplastic diseases [1].

Obatoclax (GX15-070), a pan-BCL-2 family proteins inhibitor and BH3 mimetic, exhibits a binding affinity (K_i) of 220 nM for BCL-2. It promotes autophagy-dependent cell death and cyclin D1 degradation via the proteasome. Additionally, Obatoclax demonstrates anti-cancer properties and broad-spectrum antiparasitic activity.

LDN-57444 is a reversible, competitive proteasome Uch-L1 inhibitor(IC50=0.88 μM) .

Degrasyn (WP1130) (WP1130), a specific deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor, also inhibits Bcr/Abl, which is a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT).

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.

Calpeptin is a potent, cell-permeable calpain inhibitor.

UT-34 is a selective and orally active antagonist of second-generation pan-androgen receptor (AR) and degrader(IC50s of 211.7 nM, 262.4 nM and 215.7 nM for wild-type, F876L and W741L AR, respectively), and has anti-prostate cancer efficacy.

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.

B-AP15 (NSC-687852)(NSC-687852) is a selective inhibitor of the deubiquitinating enzymes Usp14 and UCHL5 of the 26S proteasome. It blocks the deubiquitinating activity of the 26S proteasome.

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).

Pepstatin (Pepsin Inhibitor S 735A) is a specific aspartic proteases inhibitor produced by actinomycetes, and inhibits the aspartic proteases cathepsin D, pepsin and renin.

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).

ONX-0914 (PR-957) is an effective and specific immunoproteasome inhibitor, which has minimal cross-reactivity for the constitutive proteasome.

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

Bis-PEG23-endo-BCN is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.

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.

IU1(IC50=4.7 μ M), a reversible, specific human USP14 proteasome inhibitor, can penetrate the cell.

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.

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.

FmocNH-PEG4-t-butyl ester is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.

Azide-PEG16-alcohol is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.