A potent, orally bioavailable, irreversible proteasome inhibitor with potent antimyeloma activity (IC50<60 nM).

Bortezomib is a potent 20S proteasome inhibitor with Ki of 0.6 nM.

Carfilzomib is an irreversible proteasome inhibitor with an IC50 of 5 nM in ANBL-6 and RPMI 8226 cells,showed potent activity against COVID-19(SARS-COV-2).

Celastrol is a potent proteasome inhibitor for the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM.

Delanzomib(CEP-18770) is a novel orally-active inhibitor of the chymotrypsin-like activity of the proteasome that down-modulates the nuclear factor-kappaB (NF-kappaB) activity.

KZR-504 is a highly selective and orally active inhibitor of immunoproteasome low molecular mass polypeptide 2 (LMP2), with IC50s of 51 nM, 4.274 μM for LMP2 and LMP7, respectively.

MG-101 is a calpain inhibitor (IC50 = 0.09 μM) that activates p53-dependent apoptosis in tumor cell lines.

MG-132 is an inhibitor of proteasome with IC50 of 100 nM, and also inhibits calpain with IC50 of 1.2 μM.

MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM.

MLN-9708 is a proteasome inhibitor, which inhibits the activity of the proteasome, blocking the targeted proteolysis normally performed by the proteasome.

ONX 0914 is an immunoproteasome inhibitor with potential treatment applications in autoimmune disorders, such as rheumatoid arthritis, inflammatory bowel disease and lupus.

Oprozomib (ONX 0912) selectively inhibits CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.

PD 150606 is a selective, cell-permeable non-peptide calpain inhibitor (Ki values for ν and m-calpains are 0.21 and 0.37 μM respectively).

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.

PI-1840 is a potent and selective inhibitor for chymotrypsin-like (CT-L) (IC50 value = 27 ± 0.14 nM) over trypsin-like and peptidylglutamyl peptide hydrolyzing (IC50 values >100 μM) activities of the proteasome.

RA190, a bis-benzylidine piperidon, inhibits proteasome function by covalently binding to cysteine 88 of ubiquitin receptor RPN13.

TCH-165 is a specific small molecule modulator of proteasome assembly, regulates the dynamic equilibrium between the 20S and 26S proteasome complexes, favoring 20S-mediated protein degradation.

VR-23 is a Quinoline-Sulfonyl Hybrid Proteasome Inhibitor That Selectively Kills Cancer via Cyclin E–Mediated Centrosome Amplification

(1S,2S)-Bortezomib is an enantiomer of Bortezomib. Bortezomib is a cell-permeable, reversible, and selective proteasome inhibitor, and potently inhibits 20S proteasome (Ki of 0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is an anti-cancer agent and the first therapeutic proteasome inhibitor to be used in humans.

PTP1B-IN-9 is a ubiquitin-proteasome system (UPS)-stressor. PTP1B-IN-9 inhibits ubiquitin-mediated protein degradation upstream of the 20S proteasomal catalytic activites. PTP1B-IN-9 triggers a ubiquitin-proteasome-system (UPS)-stress response without affecting 20S proteasome catalytic activities. Anticancer activity.

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. MDL-28170 is also an inhibitor of γ-secretase.

(Rac)-Calpain Inhibitor XII is a reversible and selective inhibitor of calpain I (μ-calpain, Ki=19 nM), with lower affinities for calpain II (m-calpain, Ki=120 nM) and cathepsin B (Ki=750 nM). (Rac)-Calpain Inhibitor XII has been used to study the role of calpains in diverse processes, including neutrophil chemotaxis, neuronal signaling, and cardiac response to injury.

Acetyl-Calpastatin(184-210)(human) is a potent, selective and reversible calpain inhibitor with Ki values of 0.2 nM and 6 μM for μ-calpain and cathepsin L, respectively.

Acetyl-Calpastatin(184-210)(human) TFA is a potent, selective and reversible calpain inhibitor with Ki values of 0.2 nM and 6 μM for μ-calpain and cathepsin L, respectively.

PR-39, a natural proline- and arginine-rich antibacterial peptide, is a noncompetitive, reversible and allosteric proteasome inhibitor. PR-39 reversibly binds to the α7 subunit of the proteasome and blocks degradation of NF-κB inhibitor IκBα by the ubiquitin-proteasome pathway. PR-39 stimulates angiogenesis, inhibits inflammatory responses and significant reduces myocardial infarct size in mice.

PR-39 TFA, a natural proline- and arginine-rich antibacterial peptide, is a noncompetitive, reversible and allosteric proteasome inhibitor. PR-39 TFAreversibly binds to the α7 subunit of the proteasome and blocks degradation of NF-κB inhibitor IκBα by the ubiquitin-proteasome pathway. PR-39 TFA stimulates angiogenesis, inhibits inflammatory responses and significant reduces myocardial infarct size in mice.

18α-Glycyrrhetinic acid, a diet-derived compound, is an inhibitor of NF-kB and an activator of proteasome, which serves as pro-longevity and anti-aggregation factor in a multicellular organism. 18α-Glycyrrhetinic acid induces apoptosis.

KZR-616 maleate, a first-in-class immunoproteasome inhibitor, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. KZR-616 maleate has the potential for the research of multiple autoimmune diseases.

RA375 is a RPN13 (26S proteasome regulatory subunit) inhibitor. RA375 activates UPR signaling, ROS production and apoptosis. RA375 exhibits ten-fold greater activity against cancer lines than RA190, reflecting its nitro ring substituents and the addition of a chloroacetamide warhead.

Dazcapistat is a potent calpain inhibitor, with IC50s of <3 μM for calpain 1, calpain 2 and calpain 9, respectively (patent WO2018064119A1, compound 405).

Calpain Inhibitor-1 (compound 36) is a potent and selective cysteine protease calpain 1 (Cal1) inhibitor (IC50=100 nM; Ki=2.89 μM).

Calpain-2-IN-1 is a calpain-2 selective inhibitor that enhances learning & memory by prolonging ERK activation.

5-Amino-8-hydroxyquinoline (5A8HQ), a potential anticancer candidate, has promising proteasome inhibitory activity.

Dihydroeponemycin, an analogue of the antitumor and antiangiogenic natural product eponemycin, selectively targets the 20S proteasome. Dihydroeponemycin covalently modifies a subset of catalytic proteasomal subunits, binding preferentially to the IFN-gamma-inducible subunits LMP2 and LMP7. Dihydroeponemycin-mediated proteasome inhibition induces a spindle-like cellular morphological change and apoptosis.

PSI (Proteasome Inhibitor 1) is a potent proteasome inhibitor. PSI inhibits the proliferation of primary effusion lymphoma (PEL) cells. PSI has the potential for the research of Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and KSHV-associated lymphomas.

Immunoproteasome inhibitor 1 is a potent, reversible, time-independent immunoproteasome and proteasome inhibitor (Kis of 1.18, 0.27, 1.91 μM in β5c, β1i, β5i submits, respectively). Immunoproteasome inhibitor 1 can be used for the treatment of certain neoplastic diseases.

Proteasome-IN-4 is an excellent and non-covalent proteasome inhibitor (IC50=8.39 nM). Proteasome-IN-4 has potent antiproliferative activities against RPMI-8226, MM-1S and MV-4-11 cell lines. Proteasome-IN-4 can be used for cancer research.

CBK006377 (CBK77) is a small molecule inhibitor of the ubiquitin-proteasome system (UPS) with EC50 of 4.3 uM in MelJuSo Ub-YFP cells (6h treatment).CBK77 (16h treatment, 10 uM) causes an irreversible, global impairment of the UPS collapse, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death.CBK77 causes a global impairment of ubiquitin-dependent proteasomal degradation without global inhibition of proteasome or DUB activity.NAD(P)H:quinone oxidoreductase 1 (NQO1) is a critical factor for CBK77-mediated UPS impairment, CBK77 is an NQO1 substrate, efficiently metabolized by NQO1.CBK77 reduces growth of NQO1-proficient human cancer cells and xenograft tumors in mice without overt signs of toxicity.

M3258 (M 3258) is a potent, reversible, highly selective and orally acitve LMP7 inhibitor with ceullar IC50 of 4.1 nM.M3258 does not inhibit other constitutive proteasome and immunoproteasome subunits (IC50>2.5 uM).M3258 demonstrated strong antitumor efficacy in multiple myeloma xenograft models.M3258 treatment led to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells both in vitro and in vivo.M3258 showed superior antitumor efficacy in selected multiple myeloma and mantle cell lymphoma xenograft models compared with the approved nonselective proteasome inhibitors bortezomib and ixazomib.

MG-262 is a reversible proteasome inhibitor with diverse biological activities.

Suc-Gly-Gly-Phe-pNA is the chymotrypsin substrate with an Km value of 1.6 mM.

20S Proteasome activator 1 is a potent 20S proteasome activator with EC200 values of 0.3 μM, 0.7 μM and 1.8 μM for trypsin-like site, chymotrypsin-like site and caspase-like site. 20S Proteasome activator 1 translates well in a cellular system, preventing the accumulation of the pathogenic A53T mutant of α-synuclein. 20S Proteasome activator 1 can be used for researching neurodegenerative diseases.

Ac-PAL-AMC is a fluorogenic substrate specific for 20S proteasome LMP2/β1i activity.

Ac-WLA-AMC is a specific 20S constitutive proteasome β5 fluorogenic substrate.

NIC-0102 is an orally active proteasome inhibitor (pIC50=7.55) that specifically inhibits NLRP3 inflammatory vesicle activation. NIC-0102 shows potent anti-inflammatory effects in a model of dextran sulfate sodium (DSS)-induced ulcerative colitis. NIC-0102 also inhibits production of pro-IL-1β.

BT317 is a small molecule dual inhibitor of mitochondrial Lon Peptidase 1 (LonP1) and CT-L proteasome, subsequently induces ROS accumulation and autophagy-dependent cell death in high-grade IDH1 mutated astrocytoma lines.

KDT-11 is a specific, reversible peptidomimetic binder inhibitor of Rpn-13 with binding KD of 3 uM, selectively inhibit proliferation of a broad range of cancer cell lines (NCI60, IC50=5 uM), but not non-malignant cells.

TCL-1 is a non-covalent ligand targeting the Pru domain of Rpn-13, TCL-1 binds to the Pru domain at the Rpn-2 docking site, affects proteasome-mediated proteolysis.

TCL-Ester is the cell-permeable derivative of TCL-1, a non-covalent ligand targeting the Pru domain of Rpn-13.

TXS-8 is a specific, small molecule binder of Rpn-6 with KD of 14 uM, Rpn-6 is a subunit of the 19S regulatory particle (RP) of 26s proteasome.

WZ-1831 is a potent and highly selective inhibitor of human constitutive proteasome chymotryptic activity (β5c) with IC50 of 10 nM, >500-fold selectivity over β5i (IC50=7.1 uM).