lmp7

M3258 is an immunoproteasome subunit LMP7 (β5i) inhibitor, with an IC50 of 3.6 nM for LMP7 and 3.4 nM at the cellular level. In a multiple myeloma xenograft model, M3258 exhibits significant antitumor activity. In multiple myeloma cells, M3258 significantly and persistently inhibits LMP7 activity and ubiquitinated protein turnover in tumor tissues, further inducing apoptosis.

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

PR-924 is a selective inhibitor of tripeptide epoxyketone immunoproteasome subunit LMP-7 (IC50: 22 nM). PR-924 inhibits growth and triggers apoptosis in multiple myeloma (MM) cells. PR-924 has antitumor activities. PR-924 covalently modifies proteasomal N-terminal threonine active sites.

LMP7/LMP2-IN-1 (Compound 19) is an orally effective inhibitor targeting the immunoproteasome subunits LMP7 and LMP2, with respective IC50 values of 257 and 10 nM. This compound reduces the production of antibodies and downregulates the B cells in the germinal centers of the spleen and plasma cells in NP-OVA immunized mice. It has potential applications in the study of autoimmune diseases.

LMP7-IN-2 is an inhibitor of LMP7 and may be utilized in the treatment of associated inflammatory diseases and disorders [1].

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

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.

LMP744 is a DNA intercalator and Topoisomerase I (Top1) inhibitor with antitumor activity.

LMP744 hydrochloride (NSC-706744 hydrochloride) is a DNA intercalator and Topoisomerase I (Top1) inhibitor with antitumor activity. 

IndiMitecan (LMP776) is an inhibitor of topoisomerase I (Top1) with anticancer activities [1].

Immunoproteasome-IN-2 is a selective immunoproteasome inhibitor with an IC50 of 232.3 nM for the LMP7 subunit and 9384.9 nM for the β5 subunit. It additionally displays inhibitory activity against LMP2 and MECL-1 subunits. In an arthritis mouse model, Immunoproteasome-IN-2 demonstrates anti-inflammatory effects and shows low hepatotoxicity and hematotoxicity in toxicology studies, linking its LMP7/β5 selectivity to reduced systemic toxicity. Immunoproteasome-IN-2 can be utilized in arthritis-related research.

KZR-616, a first-in-class inhibitor of the immunoproteasome, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. KZR-616 has the potential for the research of multiple autoimmune diseases[1][2]. KZR-616 also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=688 nM). KZR-616 maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. KZR-616 (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1].KZR-616 is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 and PR-924 [3]. KZR-616 (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model[1]. [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem. 2018 Dec 27;61(24):11127-11143. [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685. [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646.

Zetomipzomib maleate (KZR-616), a novel immunoproteasome inhibitor, effectively and selectively inhibits the LMP7 subunit (hLMP7/mLMP7 IC50: 39/57 nM) and LMP2 subunit (hLMP7/mLMP7 IC50: 131/179 nM) of the immunoproteasome. This compound shows promising potential for research in various autoimmune diseases.

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

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].

EWFW-ACC is a tetrapeptide substrate (substrate) for the immunoproteasome, demonstrating selectivity for the LMP7 subunit.

Biotin-epoxomicin is a biotin-labeled form of epoxomicin. It acts as a high-affinity probe targeting the proteasome (Proteasome) and is capable of covalently binding to various proteasome catalytic subunits, such as LMP7, Z, and MECL1.

Biotin-(Oaa)3-epoxomicin (Compound 13) is the biotinylated active form of Epoxomicin. It serves as a high-affinity probe targeting the proteasome. Biotin-(Oaa)3-epoxomicin can covalently bind to multiple proteasome catalytic subunits, such as LMP7, Z, and MECL1.