pr-39

Antibacterial peptide. Stimulates angiogenesis and inhibits inflammatory responses by selectively blocking proteasome degradation of IκBα.

PR-39 TFA, a natural peptide rich in proline and arginine with antibacterial properties, acts as a noncompetitive, reversible, and allosteric inhibitor of the proteasome. It specifically attaches to the α7 subunit of the proteasome, preventing the degradation of the NF-κB inhibitor IκBα through the ubiquitin-proteasome pathway. Additionally, PR-39 TFA promotes angiogenesis, suppresses inflammatory responses, and notably decreases myocardial infarct size in mice [1] [2].

PR 39 (porcine) acetate is a noncompetitive, reversible and allosteric proteasome inhibitor. PR 39 (porcine) acetate reversibly binds to the α7 subunit of the proteasome and blocks degradation of NF-κB inhibitor IκBα by the ubiquitin-proteasome pathway.

TM-N1324 is a GPR39 agonist. TM-N1324 activates human GPR39 with high efficacy and potencies of 280 nM and 9 nM in the absence and presence of Zn2+, respectively. TM-N1324 has similar potencies to murine GPR39 with EC50s of 180 nM and 5 nM, respectively.

TC-G-1008 (GPR39-C3) is a zinc receptor agonist with EC50 values of 0.4 nM for rat GPR39 and 0.8 nM for human GPR39.

SPR39, a potent inhibitor of the SARS-CoV-2 main protease (Mpro), demonstrates inhibitory Ki values of 0.252 µM for SARS-CoV-2 Mpro, and 3.38 and 7.88 µM for human Cathepsin L (hCatL) and human Cathepsin B (hCatB) respectively. It exhibits antiviral properties and cytotoxicity.

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.