Expert Opinion on Therapeutic Patents最新文献

{"title":"RORγt inhibitors in clinical development for the treatment of autoimmune diseases: challenges and opportunities.","authors":"Nannan Sun, Yonghui Wang","doi":"10.1080/13543776.2025.2482936","DOIUrl":"https://doi.org/10.1080/13543776.2025.2482936","url":null,"abstract":"<p><strong>Introduction: </strong>Nuclear receptor retinoid-related orphan receptor gamma-t (RORγt) is a major transcription factor for Th17 cell differentiation and IL-17 production. RORγt has been considered as a promising drug target for the treatment of IL-17-mediated inflammatory diseases. Numerous small molecule inhibitors have been discovered, and more than twenty of RORγt inhibitors have been advanced to clinical trials. However, none of these compounds has yet achieved market approval.</p><p><strong>Areas covered: </strong>This manuscript summarizes the development of 22 clinical-stage RORγt inhibitors, including their structures, patent applications, and clinical trial status, based on publications and patents available up to November 2024.</p><p><strong>Expert opinion: </strong>The discovery of RORγt inhibitors was considered as an exciting field for the development of small molecular treatments, which has gone through a boom period in the past ten years. However, some of the leading RORγt inhibitors recently failed in clinical trials due to lack of efficacy or having some safety concerns, although a few of small molecule candidates targeting RORγt are still in trials and more in preclinical studies. Realizing the challenge, researchers started to develop different approaches such as dual targeting or exploring new indications, utilizing the potential value of RORγt inhibitors.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patenting perspective of fat mass and obesity associated protein (FTO) inhibitors: 2017-present.","authors":"Ze Dong, Yue Huang, Wenyang Xia, Yonggang Liao, Cai-Guang Yang","doi":"10.1080/13543776.2025.2477482","DOIUrl":"10.1080/13543776.2025.2477482","url":null,"abstract":"<p><strong>Introduction: </strong>The fat mass and obesity-associated protein (FTO) catalytically demethylates RNA N⁶-methyl adenosine (m⁶A) modification, dynamically regulates gene expression in eukaryotes. Interestingly, FTO is highly expressed and functions as an oncogenic factor in a wide range of cancers. Therefore, using small-molecule inhibitors to target FTO has been established as a promising therapeutic strategy for combating cancers.</p><p><strong>Areas covered: </strong>Patent literature claiming novel chemical entities as FTO inhibitors disclosed from 2017 to present is available in Espacenet, including dozens of patent documents.</p><p><strong>Expert opinion: </strong>The pivotal influence of FTO demethylase in a particular epigenetic layer of regulation of gene expression renders it promising for FTO to be a therapeutical target for many diseases, including malignant cancers. Several institutions were prompted and have patented chemical frameworks as FTO inhibitors. Remarkedly, the FTO inhibitor CS1 (Bisantrene) has advanced to clinical trials for treating acute myeloid leukemia (AML). The successful advancement of CS1 into clinical trials would continuingly stimulate researches on RNA epigenetic enzymes targeted first-in-class anticancer drug discovery.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-10"},"PeriodicalIF":5.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges, opportunities and therapeutic potential of JAK inhibitors and their derived PROTACs (2022 - 2023).","authors":"Rishi R Shah","doi":"10.1080/13543776.2025.2477486","DOIUrl":"10.1080/13543776.2025.2477486","url":null,"abstract":"<p><strong>Introduction: </strong>Since the approval of the first JAK inhibitor, ruxolitinib, in 2011, the development of JAK inhibitors has expanded significantly, with applications spanning autoimmune diseases, cancer, and inflammatory disorders. This review explores the challenges and therapeutic potential of JAK inhibitors and their evolution into proteolysis-targeting chimeras (PROTACs), which offer novel avenues for selective JAK modulation.</p><p><strong>Areas covered: </strong>This review examines recent advancements in JAK inhibitors, including their mechanism of action, structure activity relationships, clinical applications, and emerging safety concerns. Additionally, PROTAC-based strategies targeting JAK proteins are discussed, highlighting their potential advantages over traditional small-molecule inhibitors. A comprehensive patent literature search was conducted, focusing on publications and patents from 2022 to 2023. Key selection criteria included small-molecule JAK inhibitors and JAK-targeting PROTACs with associated preclinical data.</p><p><strong>Expert opinion: </strong>While JAK inhibitors have transformed the treatment of various diseases, safety concerns, including risks of venous thromboembolism and herpes zoster, pose challenges to their widespread use. The advent of JAK-targeting PROTACs represents a promising strategy to enhance selectivity and mitigate off-target effects. However, further research is needed to optimize their therapeutic potential and establish their clinical viability.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patent review of hepatitis B virus core protein allosteric modulators (2019-present).","authors":"Shuo Wang, Feiyue Ma, Kai Tang, Shujing Xu, Haiyong Jia, Xinyong Liu, Peng Zhan","doi":"10.1080/13543776.2025.2467699","DOIUrl":"10.1080/13543776.2025.2467699","url":null,"abstract":"<p><strong>Introduction: </strong>The hepatitis B virus (HBV) core protein is a significant therapeutic target due to its essential role in HBV replication. Over the past five years, numerous structurally unique CpAMs have been patented. However, no compounds have been approved due to various issues such as poor pharmacokinetics (PK) and hepatotoxicity. As a result, there is an urgent need to develop novel CpAMs without these limitations.</p><p><strong>Areas covered: </strong>This review provides a comprehensive analysis of patents related to CpAMs from 2019 to the present, with the aim of delineating the chemical evolution that has occurred in the pursuit of more promising CpAMs. The sources of patent information included databases of the European Patent Office, the China Patent Office and the U.S.A. Patent Office, while relevant research articles were accessed through PubMed.</p><p><strong>Expert opinion: </strong>During the optimization of CpAMs, striking a good balance between activity and druggability usually poses a certain challenge while the emergence of drug resistance issues further complicates the development process. A comprehensive analysis of the structural features of CpAMs and identification of essential patterns in chemical evolution can reveal common principles that improve pharmacodynamic (PD) and PK profiles, thereby facilitating the discovery of next-generation CpAMs.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-21"},"PeriodicalIF":5.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity-Preserving Discriminative Feature Selection for Disease-Specific Subtype Discovery.","authors":"Abdur Rahman M A Basher, Caleb Hallinan, Kwonmoo Lee","doi":"10.1101/2023.05.14.540686","DOIUrl":"10.1101/2023.05.14.540686","url":null,"abstract":"<p><p>The identification of disease-specific subtypes can provide valuable insights into disease progression and potential individualized therapies, important aspects of precision medicine given the complex nature of disease heterogeneity. The advent of high-throughput technologies has enabled the generation and analysis of various molecular data types, such as single-cell RNA-seq, proteomic, and imaging datasets, on a large scale. While these datasets offer opportunities for subtype discovery, they also pose challenges in finding subtype signatures due to their high dimensionality. Feature selection, a key step in the machine learning pipeline, involves selecting signatures that reduce feature size for more efficient downstream computational analysis. Although many existing methods focus on selecting features that differentiate known diseases or cell states, they often struggle to identify features that both preserve heterogeneity and reveal subtypes. To address this, we utilized deep metric learning-based feature embedding to explore the statistical properties of features crucial for preserving heterogeneity. Our analysis indicated that features with a notable difference in interquartile range (IQR) between classes hold important subtype information. Guided by this insight, we developed a statistical method called PHet (Preserving Heterogeneity), which employs iterative subsampling and differential analysis of IQR combined with Fisher's method to identify a small set of features that preserve heterogeneity and enhance subtype clustering quality. Validation on public single-cell RNA-seq and microarray datasets demonstrated PHet's ability to maintain sample heterogeneity while distinguishing known disease/cell states, with a tendency to outperform previous differential expression and outlier-based methods. Furthermore, an analysis of a single-cell RNA-seq dataset from mouse tracheal epithelial cells identified two distinct basal cell subtypes differentiating towards a luminal secretory phenotype using PHet-based features, demonstrating promising results in a real-data application. These results highlight PHet's potential to enhance our understanding of disease mechanisms and cell differentiation, contributing significantly to the field of personalized medicine.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":"6 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89169616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A patent review of CYP3A4 inhibitors (2018 - present).","authors":"Dong-Zhu Tu, Xue-Yan Hu, Jing-Xuan Lei, Shu-Yan Liu, Zhang-Ping Xiao, Ling Yang, Guang-Bo Ge","doi":"10.1080/13543776.2025.2470294","DOIUrl":"10.1080/13543776.2025.2470294","url":null,"abstract":"<p><strong>Introduction: </strong>Cytochrome P450 3A4 (CYP3A4), one of the most important xenobiotic-metabolizing enzymes, plays a central role in drug metabolism and acts as a key mediator in drug-drug interactions. CYP3A4 inhibitors can potentiate the <i>in vivo</i> therapeutic effects of CYP3A4-substrate drugs via enhancing their systematic exposure levels. Two CYP3A4 inhibitors (ritonavir and cobicistat) have already been approved for modulating the exposure levels of CYP3A4-substrate drugs.</p><p><strong>Areas covered: </strong>This review summarizes the newly patented CYP3A4 inhibitors in the period (2018-2024) by using the keywords 'CYP3A4' and 'inhibitor' in Espacenet database from academic institutions and industrial companies. The chemical structures and inhibition profiles of the patented CYP3A4 inhibitors, including the anti-CYP3A4 potency, inhibitory mechanisms, and other relevant information, are summarized and discussed.</p><p><strong>Expert opinion: </strong>Although diverse CYP3A4 inhibitors have been developed in the past few years, the development of more efficacious CYP3A4 inhibitors with favorable pharmacokinetic and safety profiles is still challenging. To maximize the benefit of CYP3A4 inhibitors, combination strategies should be used for the development of highly specific CYP3A4 inhibitors or degraders with efficacious anti-CYP3A4 effects and favorable pharmacokinetic profiles. Meanwhile, more efforts should be made to address the organ-targeting or tumor-targeting ability of CYP3A4 inhibitors for specific purposes.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-11"},"PeriodicalIF":5.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on mGlu4 modulator patents: 2017 to present.","authors":"Fahad Imtiaz Rahman, Thomas M Webster, Corey R Hopkins","doi":"10.1080/13543776.2025.2467679","DOIUrl":"10.1080/13543776.2025.2467679","url":null,"abstract":"<p><strong>Introduction: </strong>Metabotropic glutamate receptor 4 (mGluR4) regulates disease by modulating neurotransmitter release and synaptic plasticity and has been implicated in various diseases, including neurodegenerative disorders and psychiatric conditions, where its dysregulation can impact synaptic function and neuronal signaling.</p><p><strong>Areas covered: </strong>This review covers the patents and key literature concerning mGluR4 PAMs by utilizing the search engines: SciFinder, Google Patents, and PubMed from 2017 to 2024. It summarizes the key exemplified compounds, relevant SAR, and key biological data presented in the patents and primary literature. The key findings and potential path forward are also discussed.</p><p><strong>Expert opinion: </strong>The mGluR4 receptor serves as a novel target for the treatment of neurodegenerative disorders (namely Parkinson's disease), multiple sclerosis, and chronic pain along with other brain disorders. Two compounds have been advanced to early-stage clinical trials from Prexton Therapeutics and Appello Pharmaceuticals. The first compound from Prexton failed due to efficacy and the Appello compound has yet to have results disclosed. The results from this trial will be an important test for whether future mGluR4 PAMs are advanced into clinical trials.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-13"},"PeriodicalIF":5.4,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of the patent literature surrounding TRPV1 modulators.","authors":"Isabel Devesa, Gregorio Fernández-Ballester, Asia Fernandez-Carvajal, Antonio Ferrer-Montiel","doi":"10.1080/13543776.2025.2467698","DOIUrl":"10.1080/13543776.2025.2467698","url":null,"abstract":"<p><strong>Introduction: </strong>TRPV1, a pivotal therapeutic target for chronic pain and pruritus, has been validated in the pathogenesis of several pathologies from diabetes to cancer. Despite the constellation of chemical structures and strategies, none of these molecules has yet been clinically developed as a new drug application due to safety concerns, particularly in thermoregulation. Thus, clinical development of TRPV1 modulators remains a challenge.</p><p><strong>Areas covered: </strong>This review covers the patent literature on TRPV1 modulators (2019-2024, PubMed, Google Patents, and Espacenet), from orthosteric ligands to innovative compounds of biotechnological origin such as interfering RNAs or antibodies, and dual modulators that can act on TRPV1 and associated proteins in different tissues.</p><p><strong>Expert opinion: </strong>Therapeutic strategies that preferentially act on dysfunctional TRPV1 channels appear essential, along with a superior understanding of the underlying mechanisms affecting changes in core body temperature (CBT). Recent findings describing differential receptor interactions of antagonists that do not affect CBT may pave the way to the next generation of orally active TRPV1 inhibitors. Although we have thus far experienced a bitter feeling in TRPV1 drug development, the recent progress in different disciplines, including human-based preclinical models, will set an interdisciplinary approach to design and develop clinically relevant TRPV1 modulators.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-15"},"PeriodicalIF":5.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JBI-802: the first orally available LSD1/HDAC6 dual inhibitor to enter clinical trials.","authors":"Jingya Zhang, Xiangli Ren, Yihui Song, Bin Yu","doi":"10.1080/13543776.2025.2468792","DOIUrl":"10.1080/13543776.2025.2468792","url":null,"abstract":"<p><strong>Introduction: </strong>Lysine-specific demethylase 1 (LSD1) and histone deacetylase 6 (HDAC6) are key epigenetic regulators involved in histone demethylation and deacetylation processes that impact chromatin structure and gene expression. JBI-802 marks a major advancement as the first novel, orally available LSD1/HDAC6 dual inhibitor currently in clinical trials.</p><p><strong>Areas covered: </strong>This review provides a comprehensive overview of the discovery and development of JBI-802, detailing its structure-activity relationship (SARs), chemical synthesis, biological activity, and clinical progress. Other dual LSD1/HDAC6 inhibitors and the challenges are briefly discussed, underscoring the therapeutic potential of dual inhibition in disease treatment. The literature search is performed using SciFinder, Google patent, ClinicalTrials databases, and PubMed.</p><p><strong>Expert opinion: </strong>The dual LSD1/HDAC6 inhibitor JBI-802 demonstrates robust anti-proliferative activity, significant antitumor effects in multiple hematologic malignancies, and superior efficacy in combination with checkpoint inhibitors in the CT-26 syngeneic mouse model. JBI-802 is currently undergoing phase I/II clinical trials in patients with advanced solid tumors, myeloproliferative neoplasms (MPN), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with thrombocytosis. However, the potential on-target toxicity, off-target interactions and selectivity concerns deservee more attention.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-9"},"PeriodicalIF":5.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2Y₁₂R antagonists in antithrombotic therapy: a patent and literature review (2019-present).","authors":"Xin-Yu Chen, Kai Wang, Jie Jia, Xiao-Tian Kong, Huan-Qiu Li, Sheng Tian","doi":"10.1080/13543776.2025.2467683","DOIUrl":"10.1080/13543776.2025.2467683","url":null,"abstract":"<p><strong>Introduction: </strong>P2Y₁₂ receptor (P2Y₁₂R) is a G protein-coupled receptor that plays a crucial role in regulating platelet activation and aggregation. P2Y₁₂R is involved in various processes such as renal fibrosis, cancer, ischemic disease, and related complications, making it an appealing target for therapeutic interventions. Over the past decade, the discovery and development of P2Y₁₂R antagonists have significantly advanced, offering novel treatment options that improve clinical outcomes.</p><p><strong>Areas covered: </strong>This review covers P2Y₁₂R antagonists reported in patents issued in the online databases of the World Intellectual Property Organization and the European Patent Office from 2019 to 2024. This review introduces the development of existing antagonists and evaluates the therapeutic potential of these compounds.</p><p><strong>Expert opinion: </strong>Reversible P2Y₁₂R antagonists offer a potentially safer alternative to the currently dominant irreversible antagonists on the market, as they allow for more controlled platelet inhibition and can reduce the toxicity and adverse effects associated with conventional drugs. Importantly, the integration of computational drug design and molecular docking studies in the discovery and optimization of P2Y₁₂R antagonists represents a significant advancement in precision medicine. This not only provides valuable structural scaffolds but also stimulates novel ideas for developing promising drugs that are both safe and efficacious.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-18"},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}