Last update 21 Mar 2024

PMPCB

peptidase, mitochondrial processing subunit beta

Last update 21 Mar 2024

Basic Info

Synonyms

beta-MPP, MAS1, Mitochondrial-processing peptidase subunit beta

+ [5]

Introduction

Catalytic subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins (PubMed:29576218) (Probable). Preferentially, cleaves after an arginine at position P2 (By similarity). Required for PINK1 turnover by coupling PINK1 mitochondrial import and cleavage, which results in subsequent PINK1 proteolysis (PubMed:22354088).

100 Clinical Results associated with PMPCB

100 Translational Medicine associated with PMPCB

0 Patents (Medical) associated with PMPCB

1,058

Literatures (Medical) associated with PMPCB

19 Feb 2024·Journal of human genetics

Leigh syndrome with developmental regression and ataxia due to a novel splicing variant in the PMPCB gene.

Article

Author: Emma Matthews ; Ella F Whittle ; Faraan Khan ; Meriel McEntagart ; Christopher J Carroll

Only five children with pathogenic PMPCB gene variants have been described and all carried missense variants. Clinical features included a Leigh-like syndrome of developmental regression, basal ganglia lesions and ataxia with or without dystonia and epilepsy. Three of the five died in childhood and none was older than age six when described. We report the first splice site variant in the PMPCB gene in a 39-year old individual who experienced developmental regression and ataxia following otitis media in childhood. A minigene assay confirms this variant results in aberrant splicing and skipping of exon 12.

10 Jan 2024·Biomedicines

Suppression of Bcl3 Disrupts Viability of Breast Cancer Cells through Both p53-Dependent and p53-Independent Mechanisms via Loss of NF-κB Signalling.

Article

Author: Daniel J Turnham ; Hannah Smith ; Richard W E Clarkson

The NF-κB co-factor Bcl3 is a proto-oncogene that promotes breast cancer proliferation, metastasis and therapeutic resistance, yet its role in breast cancer cell survival is unclear. Here, we sought to determine the effect of Bcl3 suppression alone on breast cancer cell viability, with a view to informing future studies that aim to target Bcl3 therapeutically. Bcl3 was suppressed by siRNA in breast cancer cell lines before changes in viability, proliferation, apoptosis and senescence were examined. Bcl3 suppression significantly reduced viability and was shown to induce apoptosis in all cell lines tested, while an additional p53-dependent senescence and senescence-associated secretory phenotype was also observed in those cells with functional p53. The role of the Bcl3/NF-κB axis in this senescence response was confirmed via siRNA of the non-canonical NF-κB subunit NFKB2/p52, which resulted in increased cellular senescence and the canonical subunit NFKB1/p50, which induced the senescence-associated secretory phenotype. An analysis of clinical data showed a correlation between reduced relapse-free survival in patients that expressed high levels of Bcl3 and carried a p53 mutation. Together, these data demonstrate a dual role for Bcl3/NF-κB in the maintenance of breast cancer cell viability and suggests that targeting Bcl3 may be more beneficial to patients with tumours that lack functional p53.

01 Jan 2024·PloS one

Poly-(ADP-ribose) polymerases inhibition by olaparib attenuates activities of the NLRP3 inflammasome and of NF-κB in THP-1 monocytes.

Article

Author: Khamis Mustafa ; Ying Han ; Dan He ; Ying Wang ; Nan Niu ; Pedro A Jose ; Yinong Jiang ; Jeffrey B Kopp ; Hewang Lee ; Peng Qu

Poly-(ADP-ribose) polymerases (PARPs) are a protein family that make ADP-ribose modifications on target genes and proteins. PARP family members contribute to the pathogenesis of chronic inflammatory diseases, including atherosclerosis, in which monocytes/macrophages play important roles. PARP inhibition is protective against atherosclerosis. However, the mechanisms by which PARP inhibition exerts this beneficial effect are not well understood. Here we show that in THP-1 monocytes, inhibition of PARP by olaparib attenuated oxidized low-density lipoprotein (oxLDL)-induced protein expressions of nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing-3 (NLRP3) inflammasome components: NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1. Consistent with this effect, olaparib decreased oxLDL-enhanced interleukin (IL)-1β and IL-18 protein expression. Olaparib also decreased the oxLDL-mediated increase in mitochondrial reactive oxygen species. Similar to the effects of the NLRP3 inhibitor, MCC950, olaparib attenuated oxLDL-induced adhesion of monocytes to cultured human umbilical vein endothelial cells and reduced foam cell formation. Furthermore, olaparib attenuated the oxLDL-mediated activation of nuclear factor (NF)-κB through the oxLDL-mediated increase in IκBα phosphorylation and assembly of NF-κB subunits, demonstrated by co-immunoprecipitation of IκBα with RelA/p50 and RelB/p52 subunits. Moreover, PARP inhibition decreased oxLDL-mediated protein expression of a NF-κB target gene, VCAM1, encoding vascular cell adhesion molecule-1. This finding indicates an important role for NF-κB activity in PARP-mediated activation of the NLRP3 inflammasome. Thus, PARP inhibition by olaparib attenuates NF-κB and NLRP3 inflammasome activities, lessening monocyte cell adhesion and macrophage foam cell formation. These inhibitory effects of olaparib on NLRP3 activity potentially protect against atherosclerosis.

News (Medical) associated with PMPCB

07 Jun 2023

·www.prnewswire.com

Cholangiocarcinoma Clinical Trial Pipeline Analysis Demonstrates 65+ Key Companies at the Horizon Expected to Transform the Treatment Paradigm, Assesses DelveInsight

The prevalence of cholangiocarcinoma has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of cholangiocarcinoma and the growing research and development activities to develop novel therapies to treat cholangiocarcinoma to drive the market. The companies developing the potential therapies in the last stage of development include Eisai, Janssen Research & Development, 3D Medicines, and several others. LAS VEGAS, June 7, 2023 /PRNewswire/ -- ' Cholangiocarcinoma Pipeline Insight – 2023 ' report provides comprehensive global coverage of pipeline cholangiocarcinoma therapies in various stages of clinical development, major pharmaceutical companies working to advance the pipeline space and future growth potential of the cholangiocarcinoma pipeline domain. Key Takeaways from the Cholangiocarcinoma Pipeline Report DelveInsight's cholangiocarcinoma pipeline report depicts a robust space with 65+ active players working to develop 70+ pipeline therapies for cholangiocarcinoma treatment. Key cholangiocarcinoma companies such as Merck KGaA, Eisai Inc., Janssen Research & Development, LLC, 3D Medicines, Basilea Pharmaceutica, Hutchison Medipharma Limited, Jiangsu HengRui Medicine, TransThera Sciences, RedHill Biopharma, Eli Lilly and Company, Elevation oncology, Senhwa Biosciences, InnoCare Pharma, Genoscience Pharma, Intensity therapeutics, Elucida Oncology, GlaxoSmithKline, Verismo Therapeutics, Sirnaomics, Toray Industries, Inc, Kinnate Biopharma, Boehringer Ingelheim, Wellmarker Bio, Arbele Limited, NGM Biopharmaceuticals, Inc., Elicio Therapeutics, Xencor, Inc., Celon Pharma SA, and others are evaluating new cholangiocarcinoma drugs to improve the treatment landscape. Promising cholangiocarcinoma pipeline therapies in various stages of development include Camrelizumab, Niraparib, Irinotecan Liposome, ABC294640, Bintrafusp alfa, TT-00420, Erdafitinib, E7090, 3D185, HMPL-453, Derazantinib, Abemaciclib, Seribantumab, CX-4945, ICP-192, GNS561, INT230-6, SynKIR-110, STP705, LY3410738, TRK-950, KIN-3248, BI 905711, WM-S1-030, ARB202, NGM831, ELI-002 2P, XmAb20717, CPL304110, and others. In May 2023, Richard Kim discussed the investigation of RLY-4008 for the treatment of patients with cholangiocarcinoma harboring an FGFR2 fusion or rearrangement. RLY-4008 is a highly selective, irreversible FGFR2 inhibitor currently under evaluation in the phase 1/2 REFOCUS trial (NCT04526106). Preliminary data reported at the 2022 ESMO Congress showed that patients with FGFR inhibitor–naïve cholangiocarcinoma who had an FGFR2 fusion or rearrangement (n = 17) experienced an overall response rate of 88.2%. In April 2023, Nuvectis Pharma provided highlights from the poster presentation of NXP800 at the American Association for Cancer Research ("AACR") Annual Meeting 2023 in Orlando, FL. The robust preclinical activity demonstrated by NXP8000 in these CCA PDX models was believed to be served as good indicators for potential clinical benefit. CCA is a very difficult-to-treat disease with poor outcomes and today's results provide promise for patients in the future. In April 2023, Verismo Therapeutics received fast-track designation from the US Food and Drug Administration (FDA) for its investigational new drug, SynKIR-110.SynKIR-110 is an investigational drug to treat serious diseases and life-threatening conditions, specifically mesothelin-expressing mesothelioma, ovarian cancer, and cholangiocarcinoma. In January 2023, Taiho Oncology, Inc. announced the publication of results from the pivotal Phase 2 FOENIX*-CCA2 clinical trial of futibatinib in the January 19, 2023 issue of The New England Journal of Medicine (NEJM). In the FOENIX-CCA2 trial, futibatinib showed clinically meaningful benefit in previously treated patients with FGFR2 fusion/rearrangement-positive iCCA, including an objective response rate of 42%, as assessed by independent review, and a median response duration of 9.7 months. Treatment with futibatinib resulted in durable responses and survival that surpassed historical data with chemotherapy in patients with previously treated iCCA. In October 2022, Invitae announced a partnership with AstraZeneca to use Invitae's Ciitizen natural history data in a retrospective and prospective study of patients diagnosed with cholangiocarcinoma, a rare bile duct cancer. This partnership will enable sharing of high-quality, patient-consented data from the patient community of the Cholangiocarcinoma Foundation (CCF), a leading patient advocacy group whose mission is to find a cure and improve the quality of life for those with cholangiocarcinoma. In November 2022, The FDA granted orphan drug designation to ZB131 for treatment of cholangiocarcinoma, according to the agent's manufacturer. ZB131 (ZielBio) is a monoclonal antibody with a high affinity and specificity for cancer-specific plectin. Request a sample and discover the recent advances in cholangiocarcinoma drug treatment @ Cholangiocarcinoma Pipeline Report The cholangiocarcinoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage cholangiocarcinoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the cholangiocarcinoma clinical trial landscape. Cholangiocarcinoma Overview Cholangiocarcinoma is an epithelial cell cancer that arises from several places within the biliary network and exhibits cholangiocyte differentiation markers. The most recent anatomical classifications include intrahepatic, perihilar, and distal cholangiocarcinoma. Many occurrences of cholangiocarcinoma occur without a specific risk factor, but a variety of risk factors have been found, including primary hepatobiliary illness, genetic diseases, toxic exposures, and infections. Like many other cancers, cholangiocarcinoma develops from precursor lesions such as the more common biliary intraepithelial neoplasia and the less common intraductal papillary mucinous neoplasm. Mutations in various oncogenes and tumor suppressor genes cause the normal epithelium to become one of these premalignant lesions. Cholangiocarcinomas have mutations in genes such as RAS, BRAF, p52, SMAD4, and others, but the exact molecular mechanism has not been discovered. Basic laboratory tests for the liver should include aminotransferases, alkaline phosphatase, and total/indirect/direct bilirubin. Cholangiocarcinoma can be treated medically or surgically, although surgery is the only curative option. Find out more about drugs for cholangiocarcinoma @ New Cholangiocarcinoma Drugs A snapshot of the Cholangiocarcinoma Pipeline Drugs mentioned in the report: Learn more about the emerging cholangiocarcinoma pipeline therapies @ Cholangiocarcinoma Clinical Trials Cholangiocarcinoma Therapeutics Assessment The cholangiocarcinoma pipeline report proffers an integral view of cholangiocarcinoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Cholangiocarcinoma Pipeline Report Coverage: Global Cholangiocarcinoma Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Cholangiocarcinoma Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Cholangiocarcinoma Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravitreal, Subretinal, Topical Cholangiocarcinoma Therapeutics Assessment By Molecule Type: Monoclonal Antibody, Peptides, Polymer, Small molecule, Gene therapy Cholangiocarcinoma Therapeutics Assessment By Mechanism of Action: Type 1 fibroblast growth factor receptor antagonists, Type 3 fibroblast growth factor receptor antagonists, Type 4 fibroblast growth factor receptor antagonists, Type-2 fibroblast growth factor receptor antagonists, Programmed cell death-1 receptor antagonists, Bcr-abl tyrosine kinase inhibitors, EphA2 receptor antagonists, Platelet-derived growth factor beta receptor antagonists, Proto oncogene protein c-kit inhibitors, Src-Family kinase inhibitors, Antibody-dependent cell cytotoxicity, Programmed cell death-1 receptor antagonists, T lymphocyte stimulants, Poly(ADP-ribose) polymerase 1 inhibitors, Poly(ADP-ribose) polymerase 2 inhibitors Key Cholangiocarcinoma Companies: Merck KGaA, Eisai Inc., Janssen Research & Development, LLC, 3D Medicines, Basilea Pharmaceutica, Hutchison Medipharma Limited, Jiangsu HengRui Medicine, TransThera Sciences, RedHill Biopharma, Eli Lilly and Company, Elevation oncology, Senhwa Biosciences, InnoCare Pharma, Genoscience Pharma, Intensity therapeutics, Elucida Oncology, GlaxoSmithKline, Verismo Therapeutics, Sirnaomics, Toray Industries, Inc, Kinnate Biopharma, Boehringer Ingelheim, Wellmarker Bio, Arbele Limited, NGM Biopharmaceuticals, Inc., Elicio Therapeutics, Xencor, Inc., Celon Pharma SA, and others. Key Cholangiocarcinoma Pipeline Therapies: Camrelizumab, Niraparib, Irinotecan Liposome, ABC294640, Bintrafusp alfa, TT-00420, Erdafitinib, E7090, 3D185, HMPL-453, Derazantinib, Abemaciclib, Seribantumab, CX-4945, ICP-192, GNS561, INT230-6, SynKIR-110, STP705, LY3410738, TRK-950, KIN-3248, BI 905711, WM-S1-030, ARB202, NGM831, ELI-002 2P, XmAb20717, CPL304110, and others. Dive deep into rich insights for new drugs for cholangiocarcinoma treatment; visit @ Cholangiocarcinoma Medications Table of Contents For further information on the cholangiocarcinoma pipeline therapeutics, reach out @ Cholangiocarcinoma Drug Treatment Related Reports Cholangiocarcinoma Market Cholangiocarcinoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key cholangiocarcinoma companies, including AstraZeneca, Decalth Systems, Basilea Pharmaceutica, Taiho Oncology, Eisai Pharmaceuticals, TransThera Sciences, Incyte Corporation, Roche, among others. Cholangiocarcinoma Epidemiology Forecast Cholangiocarcinoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and cholangiocarcinoma epidemiology trends. Intrahepatic Cholangiocarcinoma Pipeline Intrahepatic Cholangiocarcinoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key intrahepatic cholangiocarcinoma companies, including Basilea Pharmaceutica, AstraZeneca, Delcath Systems Inc., Jiangsu HengRui Medicine Co., Ltd., Syndax Pharmaceuticals, Hutchison Medipharma Limited, Medivir, Newish Technology (Beijing) Co., Ltd., Relay Therapeutics, Inc., among others. Intrahepatic Cholangiocarcinoma Market Intrahepatic Cholangiocarcinoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key intrahepatic cholangiocarcinoma companies, including Kinnate Biopharma, Taiho Oncology, Inc., Sirtex Medical, Virogin Biotech Ltd, TriSalus Life Sciences, among others. Bile Duct Cancer Pipeline Bile Duct Cancer Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key bile duct cancer companies, including Merck, BMS, Elicio Therapeutics, among others. Biliary Tract Cancers Pipeline Biliary Tract Cancers Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key biliary tract cancers companies, including companies involved such as Merck, RemeGen, EMD Serono, SMT bio Co., Ltd., among others. Related Healthcare Services Healthcare Consulting Healthcare Competitive Intelligence Services Healthcare Asset Prioritization Services About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

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