Expert Opinion on Therapeutic Patents最新文献

Small molecule and peptide CXCR4 antagonists. A patent review from 2019 to 2024.

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-18 DOI: 10.1080/13543776.2025.2462848

Zafer Sahin, Yesim A Tahirovic, Jiafeng Geng, Lawrence J Wilson, Dennis C Liotta

{"title":"Small molecule and peptide CXCR4 antagonists. A patent review from 2019 to 2024.","authors":"Zafer Sahin, Yesim A Tahirovic, Jiafeng Geng, Lawrence J Wilson, Dennis C Liotta","doi":"10.1080/13543776.2025.2462848","DOIUrl":"10.1080/13543776.2025.2462848","url":null,"abstract":"Introduction: The chemokine receptor CXCR4 has been under intense study due to the central role it plays in immune system regulation and the pathology of human disease. Although the first CXCR4 drug plerixafor emerged over a decade ago (2007), recently the first peptide (motixafortide, 2023) and the first oral small molecule (mavorixafor, 2024) CXCR4 antagonists became FDA approved.Areas covered: This article describes patent documents published during the period of 2019 through 2024 for both small molecule and peptides. This IP includes few new chemotypes, with most being extensions of existing structural classes. There is also less significant IP covering peptide-based therapeutics than those covering small molecules. Notably, multiple therapeutic uses have also emerged. Patents were searched from SciFinder (CAS) and Google Patents with the term CXCR4 antagonists. Patents were selected according to whether they fit into the classification of small molecules or peptides.Expert opinion: In the last 5 years there has been significant advancement in CXCR4 antagonists as gauged by the FDA approval of two drugs. The search for second and third generation compounds will be the focus of future efforts with new uses and better properties which likely could come from some of the IP described herein.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-13"},"PeriodicalIF":5.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381980","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}

引用次数: 0

JBI-802: the first orally available LSD1/HDAC6 dual inhibitor to enter clinical trials.

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-17 DOI: 10.1080/13543776.2025.2468792

Jingya Zhang, Xiangli Ren, Yihui Song, Bin Yu

{"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":"https://doi.org/10.1080/13543776.2025.2468792","url":null,"abstract":"Introduction: 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.Areas covered: 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 their 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.Expert opinion: 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 are deserved more attention.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-17","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}

引用次数: 0

Updated patent review for hematopoietic progenitor kinase (HPK1) inhibitors and degraders (2021-present).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-16 DOI: 10.1080/13543776.2025.2462834

Ying-Hui Yuan, Jia-Ying Mao, Ji-Fan Yue, Meng-Lan He, Zi Hui, Hang Yin, Jianshe Wang, Xiang-Yang Ye

{"title":"Updated patent review for hematopoietic progenitor kinase (HPK1) inhibitors and degraders (2021-present).","authors":"Ying-Hui Yuan, Jia-Ying Mao, Ji-Fan Yue, Meng-Lan He, Zi Hui, Hang Yin, Jianshe Wang, Xiang-Yang Ye","doi":"10.1080/13543776.2025.2462834","DOIUrl":"10.1080/13543776.2025.2462834","url":null,"abstract":"Introduction: Hematopoietic progenitor cell kinase (HPK1) is a serine/threonine kinase of MAP4K family. It negatively regulates T cell receptor and B cell signal transduction. The loss of HPK1 kinase function increases the secretion of cytokines and enhances T cell signal transduction, virus clearance and tumor growth inhibition. Therefore, HPK1 is considered as a promising drug target for tumor immunotherapy.Area covered: This article surveys the patents published since 2021 aiming to analyze the structural features of scaffolds and the patent landscape. It also discusses the recent clinical developments and provides perspectives on the challenges and the future directions.Expert opinion: HPK1 kinase is a viable drug target, and there is an increasing number of clinical studies on HPK1 inhibitors. In the clinical research of HPK1 inhibitors, there are mainly two ways: monotherapy and combination therapy. In recent years, HPK1 degraders derived from PROTAC technology have shown promises along with HPK1 inhibitors. It is hopeful that small molecule inhibitors or degraders targeting HPK1 will gain FDA approval for treatment of human diseases in the near future.Databases searched and inclusive dates: A rapid survey of literature reports using keyword 'HPK1' in SciFinder® search engine yielded about 180 papers since 2021.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-22"},"PeriodicalIF":5.4,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413900","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}

引用次数: 0

Small molecules targeting immune checkpoint proteins for cancer immunotherapy: a patent and literature review (2020-2024).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-16 DOI: 10.1080/13543776.2025.2462849

Qiaohong Geng, Juanjuan Xu, Chunsheng Du, Deheng Zhang, Yanrui Jin, Jiatong Song, Wenjing Qu, Changnan Zhang, Gaoxing Su, Peifu Jiao

{"title":"Small molecules targeting immune checkpoint proteins for cancer immunotherapy: a patent and literature review (2020-2024).","authors":"Qiaohong Geng, Juanjuan Xu, Chunsheng Du, Deheng Zhang, Yanrui Jin, Jiatong Song, Wenjing Qu, Changnan Zhang, Gaoxing Su, Peifu Jiao","doi":"10.1080/13543776.2025.2462849","DOIUrl":"10.1080/13543776.2025.2462849","url":null,"abstract":"Introduction: Targeting immune checkpoint proteins (ICPs) via small molecules open a new window for cancer immunotherapy. Herein, we summarize recent advances of small molecules with novel chemical structures targeting ICPs, discusses their anti-tumor efficacies, which are important for the development of novel small molecules for cancer immunotherapy.Areas covered: In this review, the latest patents and literature were gathered through the comprehensive searches in the databases of European Patent Office (EPO), Cortellis Drug Discovery Intelligence (CDDI), PubMed and Web of Science using ICPs and compounds as key words.Expert opinion: To develop novel weapons to fight against cancer, small molecules targeting ICPs including CTLA-4, LAG-3, PD-L1, Siglec-9, TIM-3, TIGIT, and VISTA have been synthesized and evaluated in succession. Chief among them are the small molecules targeting PD-L1, which have been intensively investigated in recent years. Various in vitro assays such as ALPHA, HTRF binding assay, NFAT assay have been successfully developed to screen novel IPCs inhibitors. However, the in vivo assay, for example, using double-humanized PD-1/PD-L1 (hPD-1/hPD-L1) mouse as evaluation model, are seldom reported. Novel pharmacophores with new working mechanisms such as proteolysis targeting chimeras (PROTACs) and peptides are needed to enhance the therapeutic efficacy.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-32"},"PeriodicalIF":5.4,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188655","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}

引用次数: 0

A review of the patent literature surrounding TRPV1 modulators.

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-14 DOI: 10.1080/13543776.2025.2467698

Isabel Devesa, Gregorio Fernández-Ballester, Asia Fernandez-Carvajal, Antonio Ferrer-Montiel

{"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":"https://doi.org/10.1080/13543776.2025.2467698","url":null,"abstract":"Introduction: 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 been yet clinically developed as a new drug application due to safety concerns, particularly on thermoregulation. Thus, clinical development of TRPV1 modulators remains a challenge.Areas covered: This review covers the patent literature on TRPV1 modulators (2019-2024, Pubmed, Google Patents, and Spacenet), 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.Expert opinion: 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.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-14","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}

引用次数: 0

P2Y₁₂R antagonists in antithrombotic therapy: a patent and literature review (2019-present).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-14 DOI: 10.1080/13543776.2025.2467683

Xin-Yu Chen, Kai Wang, Jie Jia, Xiao-Tian Kong, Huan-Qiu Li, Sheng Tian

{"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":"https://doi.org/10.1080/13543776.2025.2467683","url":null,"abstract":"Introduction: 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.Areas covered: 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.Expert opinion: 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.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-14","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}

引用次数: 0

A patent review of BRD4 inhibitors (2020-present).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-14 DOI: 10.1080/13543776.2025.2463150

Yanfang Chen, Huanmin Zhou, Jiamin Yu, Jing Gao, Shengyu Xue, Hong Ding, Hua Lin, Cheng Luo

{"title":"A patent review of BRD4 inhibitors (2020-present).","authors":"Yanfang Chen, Huanmin Zhou, Jiamin Yu, Jing Gao, Shengyu Xue, Hong Ding, Hua Lin, Cheng Luo","doi":"10.1080/13543776.2025.2463150","DOIUrl":"10.1080/13543776.2025.2463150","url":null,"abstract":"Introduction: Bromodomain-containing protein 4 (BRD4) stands as a pivotal member within the Bromodomain and Extra-Terminal Domain (BET) family, contributing significantly to epigenetic control and gene expression. Given its association with various cancers, BRD4 emerges as a promising therapeutic target, suggesting a substantial role in the treatment of diverse pathological conditions.Areas covered: The present review is centered on patent applications concerning inhibitors targeting BRD4's bromodomain site, published from 2020 to present. A comprehensive evaluation was conducted on a total of 70 applications. The latest patented studies of BRD4 are summarized by using the keywords 'BRD4' in SciFinder, PubMed, and The lens Patents and databases in the year from 2020 to present.Expert opinion: Despite the substantial progress achieved in the clinical research of numerous BET bromodomain inhibitors, their development remains fraught with challenges. To mitigate the dose-limiting toxicity (DLT) and other clinical adverse effects associated with pan-BET inhibitors, current research efforts are increasingly focus on the development of selective BRD4-BD1 or -BD2 inhibitors. These selective inhibitors exhibit considerable potential as more efficacious candidate drugs, thereby paving the way for novel avenues in both fundamental and translational research within this domain.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-16"},"PeriodicalIF":5.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364208","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}

引用次数: 0

Update on mGlu4 modulator patents: 2017 to present.

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-13 DOI: 10.1080/13543776.2025.2467679

Fahad Imtiaz Rahman, Thomas M Webster, Corey R Hopkins

{"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":"https://doi.org/10.1080/13543776.2025.2467679","url":null,"abstract":"Introduction: 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.Areas covered: This review covers the patents and key literature concerning mGluR4 PAMs by utilizing the search engines: SciFinder, Google Patents, and PubMed from 2017-2024. 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.Expert opinion: 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.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-13","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}

引用次数: 0

Patenting perspective on Keap1 inhibitors (2019-2024).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-10 DOI: 10.1080/13543776.2025.2462844

Yongfu Luo, Ziyu Yang, Yuan Zhang, Shutong Jiang, Jingyu Zhu, Xiangyang Li, Qidong You, Mengchen Lu

引用次数: 0

A patent review of von Hippel-Lindau (VHL)-recruiting chemical matter: E3 ligase ligands for PROTACs and targeted protein degradation (2019-present). von Hippel-Lindau （vhl）招募化学物质：用于PROTACs和靶向蛋白降解的E3连接酶配体的专利审查（2019年至今）。

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2025-02-06 DOI: 10.1080/13543776.2024.2446232

Aina Urbina, Alex J Hallatt, Jack Robertson, Alessio Ciulli

{"title":"A patent review of von Hippel-Lindau (VHL)-recruiting chemical matter: E3 ligase ligands for PROTACs and targeted protein degradation (2019-present).","authors":"Aina Urbina, Alex J Hallatt, Jack Robertson, Alessio Ciulli","doi":"10.1080/13543776.2024.2446232","DOIUrl":"10.1080/13543776.2024.2446232","url":null,"abstract":"Introduction: The von Hippel-Lindau (VHL) E3 ubiquitin ligase has seen extensive research due to its involvement in the ubiquitin proteasome system and role as a tumor suppressor within the hypoxia signaling pathway. VHL has become an attractive target for proteolysis targeting chimeras (PROTACs), bifunctional molecules that can induce degradation of neo-substrate proteins. The development of VHL inhibitors and PROTACs has seen rapid development since disclosure of the first non-peptidic VHL ligand (2012).Areas covered: Due to the demand for more diverse and sophisticated VHL ligands that can be applied to PROTACs, the number of patents disclosed has risen significantly in the past 5 years. Herein, the wide range of VHL modifications that have been patented since 2019 is covered. Specifically, any new or unique chemical modification to established VHL ligands or PROTACs will be discussed.Expert opinion: The VHL chemical space continues to expand within the patent literature. There are exciting new modifications that can enhance the physiochemical properties of VHL PROTACs and other alterations can improve the affinity of the VHL ligand itself. Further optimization of the VHL chemical space will no doubt lead to the development of more VHL-based therapies and clinical candidates.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-42"},"PeriodicalIF":5.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002867","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}

引用次数: 0