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Last update 08 May 2025

PSMB9

Last update 08 May 2025

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 (PubMed:33727065, PubMed:34819510). 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.

Kezar Life Sciences, Inc. [+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

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

LU-001i

Target

PSMB9

Mechanism

PSMB9 inhibitors

Active Org.-

Originator Org.

University of Leiden

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with PSMB9

CTR20240905

/ TerminatedPhase 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

/ TerminatedPhase 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

227

Literatures (Medical) associated with PSMB9

24 Mar 2025·Cureus

Influence of PSMB6 and PSMB9 Genetic Polymorphisms on Bortezomib-Based Therapy Response in Newly Diagnosed Multiple Myeloma

Article

Author: Sood, Nidhi ; Hamide, Abdoul ; Dubashi, Biswajit ; Jayanthi, Mathaiyan ; Munirajan, A K

BACKGROUNDBortezomib (BTZ)-based regimens play a crucial role in the treatment of multiple myeloma (MM), significantly improving patient outcomes. BTZ, a proteasome inhibitor, interferes with cellular processes essential for cancer cell growth and survival, resulting in high response rates. Its use in initial and recurrent treatment strategies has been associated with extended disease control and improved long-term outcomes, contributing to overall survival. This study aimed to delineate the clinical characteristics of newly diagnosed MM patients and investigate the influence of single nucleotide polymorphisms (SNPs) in PSMB6 and PSMB9 genes on the risk and response to BTZ-based chemotherapy, in comparison with the control group.METHODSThis prospective study was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India, comprising 92 newly diagnosed MM cases and 92 controls. Patient selection was based on receiving first-line BTZ therapy with available outcome data. DNA was extracted from peripheral blood samples, followed by SNP analysis using real-time polymerase chain reaction (PCR) with appropriate validation and quality control measures. The patients were stratified into good responders and poor responders. The association of genetic polymorphism with the response to BTZ treatment was carried out using chi-square. Survival analysis was conducted using Kaplan-Meier to estimate the overall survival (OS) and progression-free survival (PFS).RESULTSIn our study, the median age of participants was 55 years, with a predominant 71.7% being males. Backache (66.3%) emerged as the most commonly reported symptom in patients followed by myalgia (53.3%) and bony swelling (12%). The GA+AA genotype in PSMB6 (rs3169950) was significantly more prevalent in poor responders compared to good responders (odds ratio (OR)=3.20, p=0.011), indicating a potential genetic marker for treatment response. The presence of the GA+AA genotype in PSMB6 gene rs3169950 was significantly higher among poor responders compared to good responders (OR=3.200, p=0.011). Likewise, the GA+AA genotype of the PSMB9 gene (rs17587) was predominantly observed among poor responders (OR=3.08, p=0.011). However, no differences were noted in survival analysis.CONCLUSIONThe findings of this study represent a potential breakthrough, indicating that common genetic variants may significantly influence the development of MM and impact treatment response, providing valuable insights for predicting patient outcomes with BTZ-based therapies.

01 Mar 2025·Med

DHDH-mediated D-xylose metabolism induces immune evasion in triple-negative breast cancer

Article

Author: Liu, Guang-Yu ; Gong, Yue ; Ling, Yun-Xiao ; Shao, Zhi-Ming ; Ling, Yun-xiao ; Zhao, Qian ; Wu, Si-Yu ; Liu, Guang-yu ; Jiang, Yi-Zhou ; Wu, Si-yu ; He, Li-Hua ; Wu, Huai-liang ; Ji, Peng ; Wu, Huai-Liang

BACKGROUNDAlthough the prognosis of triple-negative breast cancer (TNBC) has significantly improved in the era of immunotherapy, many TNBC patients are resistant to therapies, and their disease progresses rapidly. Deciphering the metabolic mechanisms regulating anticancer immunity will provide new insights into therapeutic strategies for TNBC.METHODSIn this study, we performed bioinformatics analysis in our multi-omics TNBC database and identified that a metabolic enzyme, dihydrodiol dehydrogenase (DHDH), might promote the phenotype of "cold tumor" in TNBC. The biological function of DHDH was verified by in vitro and in vivo functional experiments, and the potential molecular mechanism of DHDH promoting TNBC immune escape was further explored.FINDINGSMechanistically, DHDH mediated the synthesis and depletion of the substrate D-xylose and inhibited the activation of the proteasome subunit beta type 9 (PSMB9) and further induction of the immune response. We demonstrated that D-xylose supplementation could enhance the proliferation of CD8⁺ T cells and the expression of cytotoxic markers against cocultured DHDH-wild type (WT) cells. Consistently, D-xylose supplementation in vivo promoted CD8⁺ T cell infiltration and the expression of cytotoxic markers and increased the sensitivity of DHDH-overexpressing tumors to immune checkpoint blockade (ICB).CONCLUSIONSOur findings reveal that a D-xylose-regulated PSMB9-dependent pathway governs tumor-intrinsic immunogenicity and, hence, the sensitivity to ICB, which may provide approaches to promote the "cold-to-hot" transition in TNBC.FUNDINGThis study was funded by the National Key Research and Development Plan of China, Shanghai Science and Technology Commission, National Natural Science Foundation of China, and China Postdoctoral Science Foundation.

01 Mar 2025·International Immunopharmacology

A druggable targets discovery strategy for diseases (DTDS): Taking Rheumatoid arthritis as a case

Article

Author: Xu, Zhenzhen ; Yuan, Anlei ; Zheng, Lulu ; Qiao, Liansheng ; Wang, Zewen ; Liu, Kaiyang ; Zhao, Shuai ; Ren, Yue ; Zhang, Yanling ; Bi, Shijie ; Liu, Chaoqun ; Li, Beiyan

Identifying effective druggable targets with disease-specific for diseases is a tremendous challenge in new drug development. However, current studies of druggable targets identification are most based on either druggability or disease-specific, lacking a combination of two factors. To further improve the accuracy of druggable targets discovery, a druggable target discovery strategy for diseases (DTDS) was proposed, which combined druggable targets prediction by machine learning and key targets identification by tissue-level and cellular-level transcriptomics analysis. Rheumatoid arthritis (RA), an autoimmune disease that cannot be treated entirely, was taken as a case. First, the protein-protein interaction network was constructed as the disease background network, and the classification models were established based on the topological parameters of known RA-druggable targets with druggability and non-RA targets without therapeutic effects on RA. 168 potential druggable targets were predicted by the classification models from 264 RA-related targets. Subsequently, 40 RA-specific targets were identified by tissue-level and cellular-level transcriptomics analysis from 168 potential druggable targets. Most of them were RA-druggable targets except PSMB9 and PTPRC. Finally, PSMB9 and PTPRC were further verified by in vitro experiments. The results showed that the inhibitor of PSMB9 or PTPRC could effectively inhibit inflammation and abnormal proliferation of synovial cells, proving that PSMB9 and PTPRC were potential RA-druggable targets, and further indicating that DTDS had high accuracy. In conclusion, the DTDS strategy established in this study is reliable and has been proven in identification of potential RA-druggable targets, which is expected to provide ideas and methods for systematic discovery of potential druggable targets for diseases.

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