Last update 19 Sep 2024

PSMB9

Last update 19 Sep 2024

Basic Info

Synonyms

beta1i, large multifunctional peptidase 2, LMP2

+ [15]

Introduction

The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues.

Drugs associated with PSMB9

Zetomipzomib

Target

PSMB8 x PSMB9

Mechanism

PSMB8 inhibitors [+1]

Active Org.

Yunding Xinyao Pharmaceutical Technology Co., Ltd. [+2]

Originator Org.

Onyx Pharmaceuticals, Inc.

Active Indication

Hepatitis, Autoimmune [+5]

Inactive Indication

Autoimmune Haemolytic Anaemias [+1]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

LU-001i

Target

PSMB9

Mechanism

PSMB9 inhibitors

Active Org.

University of Leiden

Originator Org.

University of Leiden

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

IPSI-001

Target

PSMB9

Mechanism

PSMB9 inhibitors

Active Org.-

Originator Org.

The University of Texas MD Anderson Cancer Center

Active Indication-

Inactive Indication

Multiple Myeloma

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with PSMB9

CTR20240905 / RecruitingPhase 2

一项在活动性狼疮肾炎患者中比较 Zetomipzomib (KZR-616) 30 mg 或 60 mg 与安慰剂的疗效和安全性的 IIb 期、随机、对照、双盲、多中心研究

[Translation] A Phase IIb, Randomized, Controlled, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Zetomipzomib (KZR-616) 30 mg or 60 mg versus Placebo in Patients with Active Lupus Nephritis

评估 Zetomipzomib 在活动性 III 或 IV 型（伴或不伴 V 型；III/IV +/-V 型）狼疮肾炎 (LN) 和单纯 V 型 LN 患者中的疗效和安全性。

[Translation]

To evaluate the efficacy and safety of zetomipzomib in patients with active class III or IV (with or without class V; class III/IV +/-V) lupus nephritis (LN) and isolated class V LN.

Start Date24 Apr 2024

Sponsor / Collaborator

Yunding Xinyao Pharmaceutical Technology Co., Ltd.

NCT05781750 / RecruitingPhase 2

A Phase 2b, Randomized, Controlled Double-blind, Multicenter Study Comparing the Efficacy and Safety of Zetomipzomib (KZR-616) 30 mg or 60 mg With Placebo in Patients With Active Lupus Nephritis

The purpose of this study is to assess the efficacy and safety of zetomipzomib (30 mg or 60 mg) compared with placebo in achieving renal response after 52 weeks of treatment in patients with active lupus nephritis (LN).

Start Date03 Nov 2023

Sponsor / Collaborator

Kezar Life Sciences, Inc.

NCT05569759 / Active, not recruitingPhase 2

A Randomized, Double-blind, Placebo-controlled, Phase 2a Study With Open-label Extension to Evaluate the Safety and Efficacy of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis

This is a Phase 2a, multi-center, placebo-controlled study in which patients with autoimmune hepatitis will receive zetomipzomib or placebo in addition to standard-of-care for 24 weeks; an optional open-label extension period allows patients to receive zetomipzomib (KZR-616) for an additional 24 weeks of treatment.

Start Date23 May 2023

Sponsor / Collaborator

Kezar Life Sciences, Inc.

100 Clinical Results associated with PSMB9

100 Translational Medicine associated with PSMB9

0 Patents (Medical) associated with PSMB9

246

Literatures (Medical) associated with PSMB9

01 Aug 2024·iMeta

Cell‐type‐specific expression analysis of liver transcriptomics with clinical parameters to decipher the cause of intrahepatic inflammation in chronic hepatitis B

Article

Author: Hoffmann, Daniel ; Wang, Jun ; Lu, Mengji ; Li, Fahong ; Zhang, Jiming ; Qiu, Yuanwang ; Li, Qian ; Kitanovski, Simo ; Li, Xiaoguang ; Wang, Chen ; Zhang, Zhenfeng ; Lu, Hongzhou ; Huang, Lihua ; Zhang, Chenxia

AbstractFunctional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi‐omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population‐specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon‐stimulated genes (ISGs). Validation through multi‐immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune‐negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi‐omics analysis integrating bulk transcriptomic, single‐cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.

25 Jul 2024·Sheng wu gong cheng xue bao = Chinese journal of biotechnology

[Establishment of a stable THP-1 cell line expressing PSMB9-eGFP-His protein and detection of immunoproteasome activity].

Article

Author: Feng, Lijie ; Xu, Ping ; Zhang, Yao ; Wang, Jiahao

The ubiquitin/proteasome system (UPS) plays a crucial role in maintaining cellular protein homeostasis. The catalytic activity of proteasome in the UPS is regulated by β1 (PSMB6), β2 (PSMB7), and β5 (PSMB5) subunits. Interferon (IFN)-γ, tumor necrosis factor (TNF)-α, inflammation, and oxidative stress can induce the replacement of β1, β2, and β5 with their respective immuno-subunits β1i (PSMB9), β2i (PSMB10), and β5i (PSMB8), which can be assembled into the immunoproteasome. Compared with the standard proteasome, the immunoproteasome exerts enhanced regulatory effects on immune responses, such as processing and presenting MHC class Ⅰ antigens, production of pro-inflammatory cytokines, and T cell differentiation and proliferation. Abnormal aggregation of immunoproteasomes can cause neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To explore the function of PSMB9 after bacterial infection, we constructed a lentivirus plasmid overexpressing PSMB9-eGFP-His and transfected the plasmid into HEK293T cells for packaging by using a triple-plasmid system in this study. After screening with puromycin, we obtained a stable human leukemia monocytic THP-1 cell line expressing the fusion protein of PSMB9. Western blotting (WB) and fluorescence microscopy verified the expression of the fusion protein in the stable THP-1 cells. Quantitative PCR (qPCR) was employed to measure the copies of PSMB9-eGFP in THP-1 cells. Immunofluorescence results found that eGFP-His did not affect the subcellular localization of PSMB9. The purification with nickel affinity chromatography confirmed that the fusion protein could be assembled into the 20S immunoproteasome and exhibited cleaving activity for fluorescent peptide substrates. These results indicated that the PSMB9-eGFP fusion gene was integrated into the chromosome, and could be stably expressed in the constructed THP-1 cell line. This cell line can be utilized for the research on subcellular localization, dynamic expression, and activity of PSMB9 in live cells at different infection conditions and disease stages. It also provides a model for the stable cell lines construction of other immunoproteasome subunits PSMB8 and PSMB10.

01 Jul 2024·Acta Pharmacologica Sinica

A novel role of PSMB9 in endothelial cells and atherosclerosis: beyond its canonical function in immunoproteasome

Article

Author: Liu, Xiaolei ; Delgado, Esteban

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