In this exploratory trial, the potential anti-seizure activity of clioquinol in a small cohort of adolescents with drug-resistant epilepsy will be examined. Subjects will be exposed to clioquinol add-on for a period of maximum 8 weeks (2 weeks low dose, 6 weeks higher dose). The main hypothesis of the study is that 30% of the included subjects will be responders and that the median seizure frequency reduction will be at least 30%.

Start Date01 Mar 2022

Sponsor / Collaborator

Katholieke Universiteit Leuven

EUCTR2020-004511-27-BE / Not yet recruitingPhase 2IIT

Add-on clioquinol in drug-resistant childhood epilepsy: an exploratory study - CLIOKID: clioquinol for Drug Resistant Epilepsy in Kids

Start Date05 Aug 2021

Sponsor / Collaborator-

100 Clinical Results associated with Proteasome x HDACs

100 Translational Medicine associated with Proteasome x HDACs

0 Patents (Medical) associated with Proteasome x HDACs

395

Literatures (Medical) associated with Proteasome x HDACs

10 Oct 2024·ACS Medicinal Chemistry Letters

Design, Synthesis, and Biological Evaluation of Selective TBL1X Degraders

Article

Author: Cheng, Xiaolin ; Alinari, Lapo ; Pray, Betsy ; Li, Pui Kai ; Yang, Rui

Transducin β-like protein 1 X-linked (TBL1X) is an essential scaffold protein involved in multiple signaling pathways, such as the Wnt/β-catenin pathway, where it protects β-catenin from ubiquitination and proteasomal degradation. Recent studies, however, suggest that TBL1X might modulate Wnt-regulated genes independently of β-catenin in diffuse large B-cell lymphoma (DLBCL). Here, we developed selective TBL1X degraders against DLBCL using the Proteolysis Targeting Chimeras (PROTACs) strategy as a proof-of-concept. Eight PROTACs showed strong cytotoxic activity. Interestingly, N-linked PROTACs exhibited minimal TBL1X degradation, while most O-linked PROTACs significantly reduced TBL1X levels, suggesting the crucial role of the linker attachment site in successful TBL1X degradation. Our mechanistic study revealed that TBL1X degradation induced by TD11 relied on the formation of the ternary complex and was dependent on the proteasome. The TBL1X degraders developed in this study could be a valuable chemical tool for investigating TBL1X-related pathways.

01 Oct 2024·International Immunopharmacology

Regulation mechanism of GPS2 on PGC-1α/Drp1-mediated mitochondrial dynamics in inflammation of acute lung injury

Article

Author: Qin, Xiaofeng ; Gu, Changping ; Qiu, Lei ; Wang, Yuelan ; Zhao, Liang ; Yan, Jie ; Zhang, Yi

Acute lung injury (ALI) has been a hot topic in the field of critical care research in recent years. Mitochondrial dynamics consists of mitochondrial fusion and mitochondrial fission. Dynamin-related protein 1 (Drp1), a key molecule that regulates mitochondrial fission, is important in the oxidative stress and inflammatory response to ALI. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a core protein that mediates mitochondrial biogenesis. G-protein pathway suppressor 2 (GPS2) acts as a transcriptional cofactor with regulatory effects on nuclear-encoded mitochondrial genes. This study aimed to investigate the mechanism of PGC-1α/Drp1-mediated mitochondrial dynamics involved in ALI and to demonstrate the protective mechanism of GPS2 in regulating mitochondrial structure and function and inflammation in ALI. The ALI model was constructed using LPS-induced wild-type mice and human pulmonary microvascular endothelial cells (HPMVECs). It was found that lung injury, oxidative stress and inflammation were exacerbated in the mice ALI model and that mitochondrial structure and function were disrupted in HPMVECs. In vitro studies revealed that LPS led to the upregulated expression of Drp1 and the downregulated expression of PGC-1α and GPS2. Mitochondrial division was reduced and respiratory function was restored in Drp1 knockdown cells, which inhibited oxidative stress and inflammatory response. In addition, the overexpression of PGC-1α and GPS2 significantly inhibited the expression of Drp1, mitochondrial function was restored, and inhibited reactive oxygen species (ROS) production and inflammatory factor release. Moreover, the overexpression of GPS2 promoted the upregulated expression of PGC-1α. This mechanism was also validated in vivo, in which the low expression of GPS2 in mice resulted in the upregulated expression of Drp1 and the downregulated expression of PGC-1α, and further exacerbated LPS-induced ALI. In the present study, we also found that LPS-induced the downregulated expression of GPS2 may be associated with its increased degradation by the proteasome. Therefore, these findings revealed that GPS2 inhibited oxidative stress and inflammation by modulating PGC-1α/Drp1-mediated mitochondrial dynamics to alleviate LPS-induced ALI, which may provide a new approach to the therapeutic orientation for LPS-induced ALI.

24 Sep 2024·Current Gene Therapy

Target and Gene-Based Therapeutic Strategies against Pancreatic Cancer: Current and Future Prospects

Article

Author: Sanyal, Somali ; Singh, Sakshi ; Sanyal, Sayak ; Dwivedi, Manish ; Dwivedi, Medha

Abstract:Despite tremendous advancements in knowledge, diagnosis, and availability of both traditional and innovative treatments, pancreatic cancer remains a dangerous disease with a high death rate and dismal prognosis. The traditional strategy in adjuvant and palliative settings is still cytotoxic chemotherapy predicated on the purine derivative gemcitabine; nevertheless, there is an increasing need for new medicines that target the primary molecular pathways and pathophysiological abnormalities implicated. There is now just a tiny amount of evidence of therapeutic benefit when the targeted drug erlotinib is added to the conventional gemcitabine treatment. In preclinical and clinical trials, novel medications targeting mTOR, NF-κB, and proteasome, including the enzyme histone deacetylase, are currently being studied alongside the well-established monoclonal antibody treatments and small-molecule protein tyrosine kinase inhibitors. These novel medications may change the negative natural progression of this illness in conjunction with gene therapy and immunotherapy, both of which are undergoing clinical study. In this regard, leveraging miRNA manipulation to combat cancer is appealing due to its promise to deliver personalized treatment tailored to an individual's distinct gene or miRNA expression profile. Preclinical studies involving animals have showcased the effectiveness of miRNA-based therapies, with several of these treatments now progressing into human clinical trials for various malignancies and other medical conditions. This review describes the important developments of targeted therapeutics that are associated with pancreatic cancer and the discoveries which can help in dealing with this fatal malignancy in a more significant manner.

News (Medical) associated with Proteasome x HDACs

27 Dec 2022

·www.businesswire.com

Precision Cancer Therapeutics Markets, 2022 - Focus on Monoclonal Antibodies, Kinase Inhibitors, Angiogenesis Inhibitors, Proteasome Inhibitors, & CAR-T therapies - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Precision Cancer Therapeutics, 2022" report has been added to ResearchAndMarkets.com's offering. The analyst has watched the cancer treatment market evolve over the past two decades and evaluated the impact new technologies are making on the market. Precision Cancer Therapeutics, 2022 focuses on the expanding area of precision cancer therapies and includes current products available and discusses some of the most exciting developments in progress. The report includes statistical information for cancers by type on a global level. Specifically, cancers where there are current products available or are in development and/or have significant incidence/mortality rates are profiled. The market segments provide an overview of disease epidemiology, leading product sales, market estimates and forecasts, and competitive summary of leading providers. The report also includes a list of Phase 3 precision therapies in development. Throughout the report, several market indicators, trends and barriers are discussed. Despite advances in cancer treatment, cancer continues to affect about 18.1 million people annually, generating a significant loss of life, financial burden and overall strain on the health industry. Worldwide between 35 and 40 million people are living with cancer and nearly 10 million people lose the battle annually. The most common cancers affecting the world population include lung, breast, colon/rectum, stomach, liver, prostate, cervical, esophageal, and bladder. Cancer deaths occur in about 50% of people who develop cancer in developed countries; this is in contrast to 80% death rate in cancer patients in underdeveloped countries. Precision treatments are less invasive and less damaging to the body, and they promise improved outcomes in many cases. The demand for more effective and tolerable cancer treatments has led to the development of novel therapeutic agents that specifically target malignant cells. Today, advanced precision cancer therapies are available, and more are being developed each year. Although there are some older precision therapies on the market, the industry is now expanding the use of these treatments to better treat cancer victims. Precision treatments are less invasive and less damaging to the body, and they promise improved outcomes in many cases. Additionally, smaller areas of precision therapies are covered including mTOR inhibitors, PI3K inhibitors, PARP inhibitors, apoptosis inhibitors, histone deacetylase inhibitors, CDK inhibitors, hedgehog signaling pathway inhibitors and several others. This report covers precision cancer therapies that do at least one of the following: Block or turn off chemical signals that tell the cancer cell to grow and divide Change proteins within the cancer cells so the cells die Stop making new blood vessels to feed the cancer cells Trigger the immune system to kill the cancer cells Carry toxins to the cancer cells to kill them, but not normal cells This report Precision Cancer Therapeutics, 2022 specifically focuses on five leading segments of precision therapies: Monoclonal antibodies Kinase inhibitors Angiogenesis inhibitors Proteasome inhibitors CAR-T therapies Other precision therapies Key Topics Covered: Chapter 1: Executive Summary Overview Scope and Methodology Market Overview and Analysis Chapter 2: Introduction Global Cancer Burden Introduction to Cancer Biochemistry of Cancer Cells Causes of Cancer Growth May Shed Light on Treatment Environmental Factors, DNA, RNA Cellular Oncogenes Tumor Suppressor Genes Cancer Treatment Approaches What is Precision Cancer Therapy? Trends in Research and Development of Precision Cancer Therapeutics Monoclonal Antibodies: The Leading Area of Cancer Precision Therapy Chapter 3: Precision Cancer Therapies: Monoclonal Antibodies Monoclonal Antibody Overview Market Outlook Principal Products Avastin (bevacizumab) Blincyto (blinatuomab) Darzalex (daratumumab) Erbitux (cetuximab) Herceptin (trastuzumab) Kadcyla (ado-trastuzumab emtansine) Keytruda (pembrolizumab) Libtayo (cemiplimab-rwlc) Opdivo (nivolumab) Padcev (enfortumab vedotin-jfv) Perjeta (pertuzumab) Rituxan (rituximab) Sarclisa (isatuximab) Tivdak (tisolumab vedotin-tftv) Tecentriq (atezolizumab) Vectibix (panitumumab) Xgeva (denosumab) Yervoy (ipilimumab) Late-Stage Monoclonal Antibodies Development Market Breakdown of Monoclonal Antibodies Cancer Monoclonal Antibody Market by Target Cancer Monoclonal Antibody Market by Type Regional Market Summary Competitor Summary Merck & Co. Genentech/Roche Bristol-Myers Squibb Janssen Biotech/J&J Amgen AstraZeneca EMD Serono Chapter 4: Precision Cancer Therapies: Kinase Inhibitors Kinase Inhibitor Overview Market Outlook Principal Products Alecensa (alectinib) Alunbrig (brigatinib) Imbruvica (ibrutinib) Inlyta (axitinib) Sprycel (dasatinib) Tasigna (nilotinib) Tagrisso (osimertinib) Gleevec (imatinib) Mekinist+Tafinlar (trametinib + dabrafenib) Sutent (sunitinib) Jakafi/Jakavi (ruxolitinib) Nexavar (sorafenib) Tukysa (tucatinib) Votrient (pazopanib) Late-Stage Kinase Inhibitors Development Market Breakdown of Kinase Inhibitors Cancer Kinase Inhibitor Market by Target Cancer Kinase Inhibitor Market by Type Regional Market Summary Competitor Summary Novartis AstraZeneca AbbVie Johnson & Johnson Pfizer Bristol-Myers Squibb Roche/Genentech Chapter 5: Precision Cancer Therapies: Angiogenesis Inhibitors Angiogenesis Inhibitor Overview Market Outlook Principal Products Pomalyst/Imnovid (pomalidomide) Revlimid (lenalidomide) Thalomid (thalidomide) Zaltrap (ziv-aflibercept) Late-Stage Angiogenesis Inhibitor Phase 3 Development Regional Market Summary Competitor Summary Chapter 6: Precision Cancer Therapies: CAR-T Therapies CAR-T Overview Manufacturing Process for CAR-T Leukapheresis Activation Transduction Expansion Regulatory Developments Market Outlook Principal Products Abecma Breyanzi Carvykti Kymriah Tecartus Yescarta Late-Stage CAR-T Therapies Development Regional Market Summary Competitor Summary Chapter 7: Precision Cancer Therapies: Proteasome Inhibitors Proteasome Inhibitor Overview Market Outlook Principal Products Kyprolis (carfilzomib) Ninlaro (ixazomib) Velcade (bortezomib) Regional Market Summary Competitor Summary Takeda Amgen Chapter 8: Precision Cancer Therapies: Other Precision Therapies Other Precision Therapies Overview Market Outlook Principal Products mTOR Inhibitor Afinitor (everolimus) mTOR Inhibitor Torisel (temsirolimus) PI3K Inhibitor Zydelig PARP Inhibitor Lynparza PARP Inhibitor Zejula Apoptosis Inducer Venclexta CDK Inhibitors - Ibrance (palbociclib) CDK Inhibitors - Kisqali (ribociclib) Late-Stage Other Therapies Development Regional Market Summary Chapter 9: Market Summary Market Influences Global Demographics Aging Population Cancer: A Growing Economic Burden Cost Containment Reimbursement Landscape: A Deciding Factor for Success The Biosimilar Movement Regional Market Overview United States and Canada EMEA Asia Pacific Latin America Chapter 10: Market Participants Top 15 Overview AbbVie, Inc. Amgen Astellas Pharma U.S., Inc AstraZeneca PLC Bayer AG Bristol-Myers Squibb Company Clovis Oncology, Inc. Dendreon Pharmaceuticals LLC Eli Lilly & Company EMD Serono, Inc. (Merck KgaA) Eisai Co., Ltd. Exelixis, Inc. Gilead Sciences, Inc. GlaxoSmithKline Johnson & Johnson Merck & Co., Inc. Novartis AG Otsuka Holdings Co., Ltd. Pfizer, Inc. Puma Biotechnology, Inc. Roche (F. Hoffman-La Roche, Ltd.) Sanofi/Genzyme Seagen Inc. Takeda Oncology - Millennium Pharmaceuticals For more information about this report visit https://www.researchandmarkets.com/r/kmh6vu

ImmunotherapyASCOPhase 3

13 May 2021

·www.globenewswire.com

Worldwide Multiple Myeloma Treatment Industry to 2029 - Players Include Janssen Biotech, Bristol-Myers Squibb and Novartis Among Others

Dublin, May 13, 2021 (GLOBE NEWSWIRE) -- The "Multiple Myeloma Treatment Market Size, Market Share, Application Analysis, Regional Outlook, Growth Trends, Key Players, Competitive Strategies and Forecasts, 2021 to 2029" report has been added to ResearchAndMarkets.com's offering. This report offers strategic insights into the overall multiple myeloma treatment market along with the market size and estimates for the duration 2019 to 2029. The said research study cover in-depth analysis of multiple myeloma market segments based on type and different geographies further segmented by countries. According to myeloma UK, in myeloma, plasma cells become abnormal, multiply uncontrollably and release only one type of antibody known as paraprotein, which has no useful function. It is often through the measurement of this paraprotein that myeloma is diagnosed and monitored.For the purpose of this study, the global multiple myeloma treatment market is segmented on the basis of type into Drug Therapy, Stem cell Transplantation, Biophosphonates, Radiation Therapy, & Surgical Therapy. Drug therapy is further segmented into monoclonal antibodies, immunomodulatory drugs, proteasome inhibitors, chemotherapy, histone deacetylase inhibitor, and corticosteroids. Market size estimates and forecast for these segments for the period 2019 to 2029 are provided in terms of USD Mn along with the respective compounded annual growth rates (CAGRs) for the period 2021 to 2029, considering 2020 as the base year.The geographical segmentation of multiple myeloma treatment market comprised regions such as North America, Europe, Asia-Pacific, Latin America & Middle East and Africa. Each geographical region is further split to provide market revenue for select countries such as the U.S., Canada, U.K. Germany, China, Japan, Brazil, Mexico, Saudi Arabia, South Africa, and other countries. Market size and forecast for these segments during 2019 to 2029 and their CAGRs for the period 2021 to 2029 are provided in this report.The multiple myeloma treatment market is observed as the most diversified and competitive market comprising large number of players. The market is dominated by several players, depending on their major competencies. The key players in this market are Celgene Corporation, Janssen Biotech, Inc., Bristol-Myers Squibb Company, Novartis AG, Millennium Pharmaceuticals, Amgen, Inc., Genzyme Corporation, Juno Therapeutics, among others.Based on the type of therapy, the global multiple myeloma market is segmented as follows: Key Topics Covered: Chapter 1. PrefaceChapter 2. Executive SummaryChapter 3. Multiple Myeloma Treatment Market: Market Dynamics and Future Outlook3.1. Market Overview3.2. Multiple Myeloma: Epidemiology3.3. Multiple Myeloma Treatment: Future Trends3.4. Drivers3.5. Challenges3.6. Opportunities3.7. Attractive Investment Proposition, by Geography, 20203.8. Major Agreements, Partnerships and Collaborations3.9. Competitive Landscape3.9.1. Competitive Landscape, by Key Players, 2020Chapter 4. Global Multiple Myeloma Treatment Market, by Type, 2019 - 2029 (US$ Mn)4.1. Overview4.1.1. Attractive Investment Proposition: Global Multiple Myeloma Treatment Market, by Type4.2. Drugs Therapy4.2.1. Monoclonal Antibodies4.2.1.1. Daratumumab4.2.1.2. Elotuzumab4.2.2. Immunomodulatory Drugs4.2.2.1. Lenalidomide4.2.2.2. Pomalidomide4.2.2.3. Thalidomide4.2.3. Proteasome Inhibitors4.2.3.1. Ixazomib4.2.3.2. Bortezomib4.2.3.3. Carfilzomib4.2.4. Chemotherapy4.2.4.1. Doxorubicin HCl liposome4.2.4.2. Melphalan4.2.4.3. Cyclophosphamide4.2.5. Histone deacetylase inhibitor4.2.5.1. Panobinostat4.2.6. Corticosteroids4.2.6.1. Dexamethasone4.2.6.2. Prednisone4.3. Stem Cell Transplantation4.3.1. Allogenic Stem Cell Transplants4.3.2. Autologous Stem Cell Transplants4.4. Biophosphonates4.5. Radiation Therapy4.6. Surgical TherapyChapter 5. Global Multiple Myeloma Treatment Market: Pipeline Analysis5.1. Overview5.2. Phase III (Market estimations by 2029)5.2.1. Venetoclax (ABT-199) (AbbVie, Inc. & Genentech, Inc.)5.2.2. MLN9708 (PETHEMA Foundation; Celgene; Millennium Pharmaceuticals, Inc.)5.2.3. M-VTD-PACE & TT3-LITE Regimen (L-TT3) (University of Arkansas; Millennium Pharmaceuticals, Inc.)5.2.4. Others5.3. Phase II (Qualitative Information)5.4. Phase I (Qualitative Information)5.5. Preclinical Studies (Quantitative Information)Chapter 6. Global Multiple Myeloma Treatment Market, by Geography, 2019 - 2029 (US$ Mn)6.1. Overview6.2. North America Multiple Myeloma Treatment Market Analysis, 2019 - 20296.2.1. North America Multiple Myeloma Treatment Market, By Type, 2019 - 2029 (US$ Mn)6.2.2. North America Multiple Myeloma Treatment Market, by Country, 2019 - 2029 (US$ Mn)6.2.2.1. U.S.6.2.2.2. Canada6.3. Europe Multiple Myeloma Treatment Market Analysis, 2019 - 20296.3.1. Europe Multiple Myeloma Treatment Market, By Type, 2019 - 2029 (US$ Mn)6.3.2. Europe Multiple Myeloma Treatment Market, by Country, 2019 - 2029 (US$ Mn)6.3.2.1. U.K.6.3.2.2. Germany6.3.2.3. France6.3.2.4. Spain6.3.2.5. Italy6.3.2.6. Rest of Europe6.4. Asia Pacific Multiple Myeloma Treatment Market Analysis, 2019 - 20296.4.1. Asia Pacific Multiple Myeloma Treatment Market, By Type, 2019 - 2029 (US$ Mn)6.4.2. Asia Pacific Multiple Myeloma Treatment Market, by Country, 2019 - 2029 (US$ Mn)6.4.2.1. Japan6.4.2.2. China6.4.2.3. India6.4.2.4. Rest of APAC6.5. Latin America Multiple Myeloma Treatment Market Analysis, 2019 - 20296.5.1. Latin America Multiple Myeloma Treatment Market, By Type, 2019 - 2029 (US$ Mn)6.5.2. Latin America Multiple Myeloma Treatment Market, by Country, 2019 - 2029 (US$ Mn)6.5.2.1. Brazil6.5.2.2. Mexico6.5.2.3. Rest of Latin America6.6. Middle East & Africa (MEA) Multiple Myeloma Treatment Market Analysis, 2019 - 20296.6.1. MEA Multiple Myeloma Treatment Market, by Type, 2019 - 2029 (US$ Mn)6.6.2. MEA Multiple Myeloma Treatment Market, by Region, 2019 - 2029 (US$ Mn)6.6.2.1. UAE6.6.2.2. Saudi Arabia6.6.2.3. South Africa6.6.2.4. Rest of MEAChapter 7. Company Profiles7.1. Janssen Biotech, Inc.7.1.1. Business Description7.1.2. Financial Information (Subject to data availability)7.1.3. Product Portfolio7.1.4. Key Developments7.2. Bristol-Myers Squibb7.3. Novartis AG7.4. Millennium Pharmaceuticals7.5. Celgene Corporation7.6. Kesios Therapeutics Limited7.7. Amgen, Inc.7.8. Genzyme Corporation7.9. Juno Therapeutics7.10. Abbvie, Inc.7.11. Array BioPharma7.12. Karyopharm Therapeutics7.13. Merck KGaA7.14. Sanofi S.A7.15. Takeda Pharmaceutical Industries Ltd.For more information about this report visit

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