Proteasome Inhibitor

Aclacinomycin A (Aclarubicin) is an orally active and potent anthracycline antitumor antibiotic. Aclacinomycin A is an inhibitor of topoisomerase I and II. Aclacinomycin A inhibits synthesis of nucleic acid, especially RNA. Aclacinomycin A might inhibit the 26S protease complex as well as the ubiquitin-ATP-dependent proteolysis.

Tomatine is a glycoalkaloid, found in the tomato plant (Lycopersicon esculentum Mill.). Tomatine elicits neurotoxicity in RIP1 kinase and caspase-independent manner. Tomatine promotes the upregulation of nuclear apoptosis inducing factor (AIF) in neuroblastoma cells. Tomatine also inhibits 20S proteasome activity.

Delanzomib (CEP-18770) is a potent and orally active chymotrypsin-like activity of the proteasome inhibitor with an IC₅₀ of 3.8 nM. Delanzomib inhibits NF-κB activity, induces cancer cell apoptotic, and has strong antiangiogenic and anti-cancer activities.

Oprozomib (PR-047) is an orally bioavailable and selective peptide epoxyketone proteasome inhibitor with IC₅₀s of 36 and 82 nM for proteasome (β5) and immunoproteasome (LMP7), respectively. Oprozomib (ONX 0912) induces apoptosis in MM cells.

FiVe1 is a vimentin (VIM) inhibitor. FiVe1 binds to the rod domain of VIM, causing metaphase VIM disassembly and hyperphosphorylation at Ser56, ultimately leading to mitotic catastrophe, multinucleation, and loss of stemness. FiVe1 has anticancer activity against soft tissue sarcomas. FiVe1 increases the sensitivity of ovarian cancer to Cisplatin (HY-17394). FiVe1 can be used for researches of mesenchymal cancers (including breast cancer and soft tissue sarcoma) and ovarian cancers.

Gabexate mesylate (FOY) is is a competitive and non-antigenic synthetic inhibitor of trypsin-like serine proteinases. Gabexate mesylate inhibits human thrombin, urokinase, plasmin, and Factor Xa with K_is of 0.97, 1.3, 1.6, and 8.5 μM, respectively. Gabexate mesylate binds to human and bovine tryptase with K_is of 3.4 nM and 18 μM, respectively. Gabexate mesylate exerts an anticoagulant effect on the clotting activity of thrombin and has anti-inflammatory effect by viainhibition of NF-κB, proinflammatory cytokines, and nitric oxide. Gabexate mesylate is used for pancreatitis and disseminated intravascular coagulation.

MG-115 is a potent and reversible proteasome inhibitor, with K_is 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.

Merbromin is a mixed inhibitor of the 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2, with an IC₅₀ of 2.7 μM. Merbromin effectively inhibits the replication of the Zika virus (ZIKV) and shows anti-ZIKV activity by inhibiting ZIKVpro. Merbromin can also be used as a topical disinfectant for cuts and scrapes, and it serves as a biological dye.

K-7174 is an orally active proteasome and GATA inhibitor. K-7174 is a cell adhesion inhibitor. K-7174 induces cell apoptosis. K-7174 shows antitumor activities, it can be used for the research of cancer.

Aloin (mixture of A&B) is an orally active anthraquinone derivative isolated from Aloe vera. Aloin (mixture of A&B) mitigates airway impairment and exerts neuroprotective, anti-inflammatory, antioxidant, antibacterial, antifungal, antiviral and antitumor effects. Aloin (mixture of A&B) inhibits Clostridium histolyticum collagenase, granulocyte matrix metalloproteinases and human 20S proteasome. Aloin (mixture of A&B) upregulates the Nrf2/HO-1 pathway, suppresses the TGF-β/Smad2/3 pathway. Aloin (mixture of A&B) reduces IL-4/IL-5/IL-13 levels, and reverses oxidative stress markers (MDA, SOD, GSH). Aloin (mixture of A&B) can be used for research on chronic ulcers, burns, wounds, inflammatory and degenerative disorders, asthma and neuroblastoma.

Alloxan hydrate is a diabetogenic agent to induce diabetes. Alloxan hydrate is a proteasome inhibitor. Alloxan causes diabetes in experimental animals through its ability to destroy the insulin-secreting B-cells of the pancreas.

ALLM (Calpain inhibitor II) is a potent inhibitor of calpain and cathepsin proteases. ALLM inhibits neuronal cell death and improves chronic neurological function after spinal cord injury (SCI).

PD 151746 is a selective calpain-1 inhibitor with an IC₅₀ of 260 nM. PD 151746 binds μ-calpain Ca²⁺-binding sites, and shows selectivity over cathepsin B, papain, trypsin, thermolysin, and basal calcineurin. PD 151746 reduces Oxidized low-density lipoprotein (oxLDL)-induced cytotoxicity, apoptotic DNA fragmentation, and blocks IL-1α maturation. PD 151746 can be used for the research of atherosclerosis and psoriasis.

M3258 is an orally bioavailable, potent, reversible and highly selective immunoproteasome subunit LMP7 (β5i) inhibitor. M3258 exerts high biochemical (IC₅₀=3.6 nM) and cellular (IC₅₀=3.4 nM) potency against the LMP7 subunit. M3258 shows strong antitumor efficacy in multiple myeloma xenograft models. M3258 leads to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells.

Bortezomib (Standard) is the analytical standard of Bortezomib. This product is intended for research and analytical applications. Bortezomib (PS-341) is a reversible and selective proteasome inhibitor, and potently inhibits 20S proteasome (K_i=0.6 nM) by targeting a threonine residue. Bortezomib disrupts the cell cycle, induces apoptosis, and inhibits NF-κB. Bortezomib is the first proteasome inhibitor anticancer agent. Bortezomib can be used for the study of multiple myeloma (MM). Bortezomib effectively inhibits TREM2 expression in tumor-associated macrophages (TAMs).

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

Zetomipzomib (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=hLMP2/mLMP2) subunits of the immunoproteasome. Zetomipzomib maleate has the potential for the research of multiple autoimmune diseases.

NA-184 is a selective and brain-penetrant calpain-2 inhibitor with an IC₅₀ of 134 nM for mouse calpain-2. NA-184 has weak inhibitory activity on calpain-1 (IC₅₀ of 2826 nM). NA-184 does not exhibit significant inhibition on a variety of other cysteine-, serine- or metallo-proteases. NA-184 shows significant neuroprotection and can be used for the study of traumatic brain injury (TBI).

10-Undecenoic acid (Undecylenic acid) is an antifungal agent. 10-Undecenoic acid inhibits Aβ oligomerization, scavenges ROS and inhibits μ-calpain activity. 10-Undecenoic acid has neuroprotective effects. 10-Undecenoic acid has anticancer effects on a variety of tumors. 10-Undecenoic acid inhibits C. albicans biofilm formation and MRSA infection. 10-Undecenoic acid inhibits quorum sensing signals of Bacillus subtilis and Pseudomonas aeruginosa.

VR23 is a small molecule that potently inhibits the activities of trypsin-like proteasomes (IC₅₀=1 nM), chymotrypsin-like proteasomes (IC₅₀=50-100 nM), and caspase-like proteasomes (IC₅₀=3 μM).