Expert Opinion on Therapeutic Patents最新文献

Selective JAK1 inhibitors and the therapeutic applications thereof: a patent review (2016-2023).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-25 DOI: 10.1080/13543776.2024.2446223

Yuhui Gao, Li Lan, Cheng Wang, Yuwei Wang, Lei Shi, Liping Sun

{"title":"Selective JAK1 inhibitors and the therapeutic applications thereof: a patent review (2016-2023).","authors":"Yuhui Gao, Li Lan, Cheng Wang, Yuwei Wang, Lei Shi, Liping Sun","doi":"10.1080/13543776.2024.2446223","DOIUrl":"10.1080/13543776.2024.2446223","url":null,"abstract":"Introduction: The family of Janus kinases (JAKs) consists of four intracellular non-receptor tyrosine kinases: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Among these four subtypes, JAK1 is the only isoform that can form heterodimers with all three JAKs, and JAK1 dysfunction can lead to inflammation and severe autoimmune diseases. Interest in JAK1 inhibitors has grown tremendously, and the number of inhibitors targeting JAK1 continues to rise annually.Areas covered: This paper reviews JAK1 small molecule inhibitors that were reported in patent literature from January 2016 to December 2023. Web of Science, SciFinder, PubMed, WIPO, EPO, USPTO, and CNIPA databases were used for searching the literature and patents for JAK1 inhibitors.Expert opinion: JAK1 inhibitors show great promise in treating cytokine dysregulated disorders; nevertheless, nonselective JAK1 inhibitors have more severe side effects, which restricts the therapy's safety and use. Therefore, developing highly selective JAK1 inhibitors can mitigate potential risks and lead to next-generation therapies with improved efficacy and safety profiles.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-15"},"PeriodicalIF":5.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881254","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 on arachidonic acid lipoxygenase (LOX) inhibitors for the treatment of neurodegenerative diseases (2018-present)".

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-24 DOI: 10.1080/13543776.2024.2447067

Danai-Eleni Vergini, Dimitra Hadjipavlou-Litina

{"title":"\"A patent review on arachidonic acid lipoxygenase (LOX) inhibitors for the treatment of neurodegenerative diseases (2018-present)\".","authors":"Danai-Eleni Vergini, Dimitra Hadjipavlou-Litina","doi":"10.1080/13543776.2024.2447067","DOIUrl":"https://doi.org/10.1080/13543776.2024.2447067","url":null,"abstract":"Introduction: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD) and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid Lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases.Areas covered: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors. A survey of patent publications from 2018 to present, taken from Google Scholar, Espanet, Web of Science, Drugbank, Scopus, or PubMed is analyzed.Expert opinion: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity, bioavailability and drug-likeness, the mechanism of action in different animals and humans, evaluation of more efficient and selective biological tests; (ii) synthetic methods outbalance in the discovery and production of ALOX inhibitors with greater selectivity. Several ALOX inhibitors show promising results for the treatment of neurological disorders. Their clinical evaluation will be critical to assess therapeutic utility. The compounds for which the mechanism of action and their bioavailability are well defined can be used as lead compounds for the treatment of neurodegenerative diseases.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880980","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

Strategies for the treatment of acute myeloid leukemia with FLT3 mutations: a patent review.

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-24 DOI: 10.1080/13543776.2024.2446224

Lukas Gorecki, Eva Reznickova, Vladimir Krystof, Martina Rezacova, Martina Ceckova, Jan Korabecny

{"title":"Strategies for the treatment of acute myeloid leukemia with FLT3 mutations: a patent review.","authors":"Lukas Gorecki, Eva Reznickova, Vladimir Krystof, Martina Rezacova, Martina Ceckova, Jan Korabecny","doi":"10.1080/13543776.2024.2446224","DOIUrl":"https://doi.org/10.1080/13543776.2024.2446224","url":null,"abstract":"Introduction: Approximately one-third of all AML patients have a mutation in the Fms-like tyrosine kinase 3 (FLT3) gene, which is associated with a poor prognosis in these individuals. The 2017 approval of midostaurin, the first FLT3 inhibitor, spurred extensive development of more potent and selective inhibitors with an improved safety profile.Areas covered: This review analyzes patent inventions for the treatment of AML using FLT3 inhibitors, covering developments from the earliest to the most recent, disclosed in 2024. Our search using the global Espacenet database identified numerous compounds with low nanomolar inhibitory concentrations against FLT3-ITD and FLT3-TKD mutants. These compounds have shown promise in preclinical studies. Co-inhibition strategies and combinatorial therapies to overcome resistance and enhance anti-leukemic efficacy are also discussed.Expert opinion: Recent patents highlight advances in the field of FLT3 inhibitors with a focus on overcoming resistance, improving selectivity and potency. Future strategies may include third-generation inhibitors such as type III allosteric inhibitors, irreversible inhibitors, or PROTACs. Personalized medicine approaches utilizing genetic profiling to tailor therapies are emphasized. Exploration of novel combination regimens with emerging therapies like CAR T-cell therapy, immune checkpoint inhibitors and small molecules targeting critical AML pathways is ongoing to further enhance anti-leukemic efficacy.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881469","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

WD repeat domain 5 (WDR5) inhibitors: a patent review (2016-present).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-22 DOI: 10.1080/13543776.2024.2441658

Jesse A Coker, Shaun R Stauffer

{"title":"WD repeat domain 5 (WDR5) inhibitors: a patent review (2016-present).","authors":"Jesse A Coker, Shaun R Stauffer","doi":"10.1080/13543776.2024.2441658","DOIUrl":"10.1080/13543776.2024.2441658","url":null,"abstract":"Introduction: WDR5 is an epigenetic scaffolding protein that has attracted significant interest as an anti-cancer drug target, especially in MLL-rearranged leukemias. The most druggable 'WIN-site' on WDR5, which tethers WDR5 to chromatin, has been successfully targeted with multiple classes of exquisitely potent small-molecule protein-protein interaction inhibitors. Earlier progress has also been made on the development of WDR5 degraders and inhibitors at the 'WBM-site' on the opposite face of WDR5.Areas covered: Based on an international survey of the patent literature using SciFinder from 2016-2024, herein we provide a comprehensive account of the chemical matter targeting WDR5, with a particular focus on proprietary compounds that are underreported in the existing academic literature. Our survey illuminates challenges for the field to overcome: a broad lack of chemical diversity, confusion about the molecular mechanism of WIN-site inhibitors, a paucity of brain-penetrant scaffolds despite emerging evidence of activity in brain cancers, sparse pharmacokinetic, metabolic, and disposition characterization, and the absence of safety or efficacy data in humans.Expert opinion: It is our opinion that the best-in-class WIN-site inhibitors (from the imidazole class) merit advancement into clinical testing, likely against leukemia, which should provide much-needed clarity about the exciting but unproven potential of WDR5 as a next-generation therapeutic target.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1-15"},"PeriodicalIF":5.4,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871906","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 mitogen-activated protein kinase-interacting kinases (MNKs) modulators (2019-present).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-21 DOI: 10.1080/13543776.2024.2446225

Qiang Li, Xiang Chen, Mingzhi Su, Yue-Wei Guo, Xin Jin

{"title":"A patent review of mitogen-activated protein kinase-interacting kinases (MNKs) modulators (2019-present).","authors":"Qiang Li, Xiang Chen, Mingzhi Su, Yue-Wei Guo, Xin Jin","doi":"10.1080/13543776.2024.2446225","DOIUrl":"https://doi.org/10.1080/13543776.2024.2446225","url":null,"abstract":"Introduction: The mitogen-activated protein kinase interacting kinases (MNKs) modulate protein translation through the phosphorylation of eukaryotic initiation factor 4E (eIF4E) at serine 209, which is crucial for tumorigenesis but dispensable for normal development. MNKs are implicated in various pathological processes, including inflammation, obesity, cancer, etc. Thus, MNKs are considered as potential drug targets and the development of potent and selective MNK inhibitors is a current research focus.Areas covered: This review covers inhibitors of MNKs reported in patents published in the online databases of the World Intellectual Property Organization and European Patent Office from 2019-2024. This review provides a landscape of available inhibitors, including their chemical structures, activity, and stage of development.Expert opinion: In recent years, highly potent and selective inhibitors have been discovered and many of them show promising results in several preclinical cancer models. The majority of small-molecule inhibitors developed recently, similarly to the structure of eFT508 and ETC-206. Also, some new skeletons were disclosed and showed novel mechanisms, including non-traditional ATP competition and induced protein degradation by proteolysis targeting chimeras. Ongoing preclinical research and clinical trials will provide us more information on these new compounds and MNKs novel functions beyond cancer.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871904","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 small molecular inhibitors targeting EGFR exon 20 insertion (Ex20ins) (2019-present).

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-21 DOI: 10.1080/13543776.2024.2446220

Wenjian Zhu, Junping Pei, Xiaoyun Lu

{"title":"A patent review of small molecular inhibitors targeting EGFR exon 20 insertion (Ex20ins) (2019-present).","authors":"Wenjian Zhu, Junping Pei, Xiaoyun Lu","doi":"10.1080/13543776.2024.2446220","DOIUrl":"https://doi.org/10.1080/13543776.2024.2446220","url":null,"abstract":"Introduction: Mutations in epidermal growth factor receptor (EGFR) kinase domain consistently activate downstream signaling pathways, such as the PI3K/AKT/mTOR and RAS/RAF/MEK, thereby promoting tumor growth. Although the majority of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations are sensitive to existing EGFR tyrosine kinase inhibitors (EGFR-TKIs), there remains an unmet clinical need for effective therapies targeting EGFR Ex20ins mutations, making direct targeting EGFR Ex20ins mutations a promising therapeutic strategy.Areas covered: This review covers the progress of clinical studies targeting EGFR Ex20ins inhibitors and summarizes recent (1 January 2019 - 30 April 2024) patents disclosing EGFR Ex20ins inhibitors available in the Espacenet and CAS SciFinder databases.Expert opinion: An increasing number of EGFR Ex20ins inhibitors are being developed and reported. Existing inhibitors are focused on enhancing the efficacy of EGFR Ex20ins inhibitors and addressing the challenge of targeted resistance by optimizing the second - or third-generation EGFR inhibitors and developing innovative skeleton molecules. Moreover, the development of targeted protein degraders, allosteric inhibitors, and combination therapies provide additional approaches to address EGFR Ex20ins mutations. However, bypass resistance, selectivity, and drug sensitivity still pose challenges in this field.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871905","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

An updated patent review of SOS1 inhibitors (2022-present). SOS1 抑制剂最新专利回顾（2022 年至今）。

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1080/13543776.2024.2419825

Guizhen Zhou, Chuan Zhou, Xinyi Ma, Jiahang Xu, Zehui Zhou, Tianfeng Xu, Mingyue Zheng, Sulin Zhang

{"title":"An updated patent review of SOS1 inhibitors (2022-present).","authors":"Guizhen Zhou, Chuan Zhou, Xinyi Ma, Jiahang Xu, Zehui Zhou, Tianfeng Xu, Mingyue Zheng, Sulin Zhang","doi":"10.1080/13543776.2024.2419825","DOIUrl":"10.1080/13543776.2024.2419825","url":null,"abstract":"Introduction: SOS1 is a crucial guanine nucleotide exchange factor for KRAS. It facilitates the transition of KRAS from inactive GDP-bound state to active GTP-bound state. The activation of KRAS triggers downstream signaling pathways, promoting tumor initiation and progression. Inhibiting SOS1 to prevent KRAS activation is an effective strategy for treating tumors driven by KRAS.Areas covered: This review identified patents claiming to be SOS1 inhibitors or SOS1-KRAS interaction modulators published between January 2022 and June 2024 using Cortellis Drug Discovery Intelligence. A total of 15 patent applications from 5 different applicants were assessed.Expert opinions: In KRAS-driven tumors, inhibiting SOS1 significantly affect cell proliferation and migration by modulating the RAS/MAPK and PI3K/AKT/mTOR signaling pathways. Since 2022, numerous patents for SOS1 inhibitors have been published. The majority of SOS1 inhibitors are currently in the preclinical phase of development, with only a few progressing to clinical trials. However, these inhibitors face significant challenges in clinical studies, including limited efficacy of monotherapies, safety concerns, and the necessity to enhance PK properties. Despite their excellent in vitro performance, SOS1 inhibitors must address issues related to safety, pharmacokinetics, and pharmacodynamics in clinical applications.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1199-1213"},"PeriodicalIF":5.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461593","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

Mycobacterium tuberculosis inhibitors: an updated patent review (2021-present). 结核分枝杆菌抑制剂：最新专利回顾（2021 年至今）。

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-01 Epub Date: 2024-11-18 DOI: 10.1080/13543776.2024.2419826

Salvucci Benedetta, Francesco Vallini, Michela Guida, Chiara Tammaro, Mariangela Biava, Giovanna Poce

{"title":"Mycobacterium tuberculosis inhibitors: an updated patent review (2021-present).","authors":"Salvucci Benedetta, Francesco Vallini, Michela Guida, Chiara Tammaro, Mariangela Biava, Giovanna Poce","doi":"10.1080/13543776.2024.2419826","DOIUrl":"10.1080/13543776.2024.2419826","url":null,"abstract":"Introduction: Tuberculosis (TB) remains a major global health issue, causing around 10 million new cases and 1.3 million deaths in 2022. The challenge is compounded by multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB strains, and co-infection with HIV.Areas covered: The present review examines significant patent literature on TB chemotherapeutics from September 2021 to the present using the following databases, reaxys, google patent and espacenet. Only patents reporting compounds with a minimum inhibitory concentration (MIC) on whole Mycobacterium tuberculosis cells of ≤5 µM were selected for review.Expert opinion: The fight against TB is advancing with the development of promising new compounds due to the challenge of drug-resistant strains. Notable among those reviewed in this paper are the benzothiazinones, showing high efficacy against both drug-sensitive and resistant TB strains. Additionally, Q203 analogues, demonstrate strong antitubercular activity, good microsomal stability, and favorable safety profiles. Finally, LysRS inhibitors also show significant promise in vivo models. These advancements underscore the importance of novel targets and innovative strategies in developing effective, resistance-resistant TB treatments.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1215-1230"},"PeriodicalIF":5.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461591","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

Coumarin derivatives as therapeutic candidates: a review of their updated patents (2017-present). 作为候选疗法的香豆素衍生物：其最新专利回顾（2017 年至今）。

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1080/13543776.2024.2419827

Kalfagianni Malamati-Konstantina, Hadjipavlou-Litina Dimitra

{"title":"Coumarin derivatives as therapeutic candidates: a review of their updated patents (2017-present).","authors":"Kalfagianni Malamati-Konstantina, Hadjipavlou-Litina Dimitra","doi":"10.1080/13543776.2024.2419827","DOIUrl":"10.1080/13543776.2024.2419827","url":null,"abstract":"Introduction: Coumarins constitute a family of heterocyclic compounds that have been extensively studied as possible drugs in the pharmaceutical research to support human health.Areas covered in this review: A survey of patent publications from 2017 to mid-2024, taken from Google Scholar, Web of Science, Scopus, or PubMed analyzes coumarins and their derivatives. It covers synthetic methods, hybridization techniques, and assessments of their biological effects in laboratory and biological studies, such as cytotoxic, antitumor, anticancer, cardiovascular, anti-atheromatic, antidiabetic, anti-asthmatic and antioxidant properties. Additionally, it presents and discusses several pharmaceutical applications for treatment and compositions involving these compounds. Structural activity relationships and mechanism of action are presented and discussed.Expert opinion: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity, bioavailability and drug-likeness, the mechanism of action in animals and humans, evaluation of more efficient and selective biological tests; (ii) synthetic technique outbalance in the discovery and production of coumarins with greater selectivity. Their clinical evaluation will be critical to assess therapeutic utility. The coumarins, for which extended biological investigations confirmed their mechanism of action, can serve as lead or hit structures for the design of new libraries with more potent molecules.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1231-1254"},"PeriodicalIF":5.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497788","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

An update patent review of MDM2-p53 interaction inhibitors (2019-2023). MDM2-p53相互作用抑制剂的最新专利综述（2019-2023）。

IF 5.4 2区医学

Expert Opinion on Therapeutic Patents Pub Date : 2024-12-01 Epub Date: 2024-11-28 DOI: 10.1080/13543776.2024.2419836

Aleksandra Twarda-Clapa

{"title":"An update patent review of MDM2-p53 interaction inhibitors (2019-2023).","authors":"Aleksandra Twarda-Clapa","doi":"10.1080/13543776.2024.2419836","DOIUrl":"10.1080/13543776.2024.2419836","url":null,"abstract":"Introduction: The activity of the major tumor suppressor protein p53 is disrupted in nearly all human cancer types, either by mutations in TP53 gene or by overexpression of its negative regulator, Mouse Double Minute 2 (MDM2). The release of p53 from MDM2 and its homolog MDM4 with inhibitors based on different chemistries opened up a prospect for a broad, non-genotoxic anticancer therapy.Areas covered: This article reviews the patents and patent applications between years 2019 and 2023 in the field of MDM2-p53 interaction inhibitors. The newly reported molecules searched in Espacenet, Google Patents, and PubMed were grouped into five general categories: compounds having single-ring, multi-ring, or spiro-oxindole scaffolds, peptide derivatives, and proteolysis-targeting chimeras (PROTACs). The article also presents the progress of MDM2 antagonists of various structures in recruiting or completed cancer clinical trials.Expert opinion: Despite 20 years of intensive studies after the discovery of the first-in-class small-molecule inhibitor, Nutlin-3, no drugs targeting MDM2-p53 interaction have reached the market. Nevertheless, more than 10 compounds are still being evaluated in clinics, both as standalone drugs and in combinations with other targeted therapies or standard chemotherapy agents, including two inhibitors in phase 3 studies and two compounds granted orphan-drug/fast-track designation by the FDA.","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"1177-1198"},"PeriodicalIF":5.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461592","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