lmp2

UK-101 是一种强效且具有选择性的免疫蛋白酶体 LMP2 的抑制剂 ，对 β1i (LMP2) 、 β1c (LMP2) 和 β5 (LMP2) 具有抑制作用，IC50 为 104nM 、15 μM 和 1 μM 。UK-101 对 β1i 的亲和力比β1c 和 β5 亚基分布高的 144 倍和 10 倍。UK-101 可诱导细胞凋亡且可用于研究前列腺癌的相关疾病。

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.

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).

LMP7 LMP2-IN-1(Compound 19)作为口服有效的LMP7和LMP2免疫蛋白酶体亚基抑制剂,IC50值分别为257 nM和10 nM.本化合物能有效降低抗体生成,并减少NP-OVA免疫小鼠脾脏中生发中心B细胞和血浆细胞的数量,适用于自身免疫性疾病的相关研究.

ML604440 是一种特异性的、有效的、细胞可渗透的蛋白酶体 β1i (LMP2) 亚基抑制剂，能够破坏 MHC I 类细胞表面表达，IL-6 分泌以及 naïve T helper 向 17 T helper 细胞的分化。它可以改善实验性结肠炎和 EAE 疾病。

D-Pyrohomoglutamic acid is a building block. It has been used in the synthesis of immunoproteasome low molecular mass polypeptide 2 (LMP2) subunit inhibitors and is a component of substance P peptide analogs.

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.

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.

Ac-PAL-AMC is a fluorogenic substrate for the β1i LMP2 subunit of the 20S immunoproteasome. Upon cleavage, 7-amino-4-methylcoumarin (AMC) is released and its fluorescence can be used to quantify the activity of the β1i LMP2 subunit of the 20S immunoproteasome. Ac-PAL-AMC is selective for the immunoproteasome over the constitutive proteasome. AMC displays excitation emission maxima of 351 430 nm, respectively.

DB-310 is a novel LMP2 inhibitor as a potential treatment for Alzheimer's disease.