Mohammad Mahboubi-Rabbani, Amir Hossein Abdolghaffari, Mahsa Ghesmati, Ali Amini, Afshin Zarghi
{"title":"Selective COX-2 inhibitors as anticancer agents: a patent review (2018-2023).","authors":"Mohammad Mahboubi-Rabbani, Amir Hossein Abdolghaffari, Mahsa Ghesmati, Ali Amini, Afshin Zarghi","doi":"10.1080/13543776.2024.2373771","DOIUrl":"10.1080/13543776.2024.2373771","url":null,"abstract":"<p><strong>Introduction: </strong>COX-2 is a crucial enzyme in the manufacture of prostaglandins. The enzyme's metabolites might have an important function as regulators of the inflammatory response and other medical conditions such as cancer. Selective COX-2 inhibitors are believed to enhance or reverse the response of cancer chemotherapeutics.</p><p><strong>Areas covered: </strong>This study addresses the chemical structures as well as the antitumor activity of new COX-2 inhibitors produced in the recent five years, aiming to provide an insight into the mechanism of COX-2 induced PGE<sub>2</sub> powerful signal in cancer development.</p><p><strong>Expert opinion: </strong>The significance of selective COX-2 inhibitors as an efficient superfamily of compounds with anti-inflammatory, anti-Alzheimer's, anti-Parkinson's disease, and anticancer properties has piqued the passion of academics in the field of drug development. Long-term usage of selective COX-2 inhibitors, such as celecoxib has been proven in clinical trials to lower the incidence of several human malignancies. Furthermore, celecoxib has the potential to greatly increase the effectiveness of chemotherapy. Our extensive understanding of selective COX-2 inhibitor SAR may aid in the development of safer and more effective selective COX-2 inhibitors as cancer chemopreventive agents. This review focuses on the different structural classes of selective COX-2 inhibitors, with a particular emphasis on their SAR.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"733-757"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491528","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}
Shirong Bian, Ru Zhang, Jianyu Nie, Mingxing Zhu, Zhouling Xie, Chenzhong Liao, Qin Wang
{"title":"Progress with polo-like kinase (PLK) inhibitors: a patent review (2018-present).","authors":"Shirong Bian, Ru Zhang, Jianyu Nie, Mingxing Zhu, Zhouling Xie, Chenzhong Liao, Qin Wang","doi":"10.1080/13543776.2024.2379924","DOIUrl":"10.1080/13543776.2024.2379924","url":null,"abstract":"<p><strong>Introduction: </strong>Polo-like kinases (PLKs) have five isoforms, all of which play crucial roles in cell cycle and cell proliferation, offering opportunities for drug design and treatment of cancers and other related diseases. Notably, PLK1 and PLK4 have been extensively investigated as cancer drug targets. One distinctive feature of PLKs is the presence of a unique polo-box domain (PBD), which regulates kinase activity and subcellular localization. This provides possibilities for specifically targeting PLKs.</p><p><strong>Area covered: </strong>This article provides an overview of the roles of PLKs in various cancers and related diseases, as well as the drug development involving PLKs, with a particular focus on PLK1 and PLK4. It summarizes the PLK1 and PLK4 inhibitors that have been disclosed in patents or literature (from 2018 - present), which were sourced from SciFinder and WIPO database.</p><p><strong>Expert opinion: </strong>After two decades of drug development on PLKs, several drugs progressed into clinical trials for the treatment of many cancers; however, none of them has been approved yet. Further elucidating the mechanisms of PLKs and identifying and developing highly selective ATP-competitive inhibitors, highly potent drug-like PBD inhibitors, degraders, etc. may provide new opportunities for cancer therapy and the treatment for several nononcologic diseases. PLKs inhibition-based combination therapies can be another helpful strategy.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"789-806"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590093","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}
Xiaoling Huang, Shidi Xu, Lei Duan, Shan Xu, Wufu Zhu
{"title":"A patent review of small molecule CDK4/6 inhibitors in the treatment of cancer: 2020-present.","authors":"Xiaoling Huang, Shidi Xu, Lei Duan, Shan Xu, Wufu Zhu","doi":"10.1080/13543776.2024.2379926","DOIUrl":"10.1080/13543776.2024.2379926","url":null,"abstract":"<p><strong>Introduction: </strong>Cyclin-dependent protein kinase 4/6 (CDK4/6) is a class of serine/threonine protein kinases that plays a key role in the regulation of the cell cycle. CDK4/6 is highly expressed in cancers such as breast cancer, melanoma, and non-small cell lung cancer (NSCLC). Currently, a variety of CDK4/6 inhibitors have been developed, aiming to develop effective inhibitors to solve CDK4/6 resistance and toxicity.</p><p><strong>Areas covered: </strong>This article searches patents through Espacenet and reviews the development of widely studied CDK inhibitors and FDA-approved CDK4/6 inhibitors, as well as the latest progress of patented inhibitors with good inhibitory activity against CDK4/6 from 2020 to now.</p><p><strong>Expert opinion: </strong>CDK4/6 is highly expressed in many tumors and has become an important anti-tumor target. Among the patents from 2020 to the present, many inhibitors have good kinase inhibitory effects on CDK4/6 and also show great development potential in anti-tumor. However, there is still an urgent need to develop novel CDK4/6 inhibitors that address challenges such as drug resistance, toxicity, and selectivity.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"825-842"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619789","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}
Margaux Morez, Antonio Jesús Lara Ordóñez, Patricia Melnyk, Maxime Liberelle, Nicolas Lebègue, Jean-Marc Taymans
{"title":"Leucine-rich repeat kinase 2 (LRRK2) inhibitors for Parkinson's disease: a patent review of the literature to date.","authors":"Margaux Morez, Antonio Jesús Lara Ordóñez, Patricia Melnyk, Maxime Liberelle, Nicolas Lebègue, Jean-Marc Taymans","doi":"10.1080/13543776.2024.2378076","DOIUrl":"10.1080/13543776.2024.2378076","url":null,"abstract":"<p><strong>Introduction: </strong>Nearly two decades after leucine rich repeat kinase 2 (LRRK2) was discovered as a genetic determinant of Parkinson's disease (PD), LRRK2 has emerged a priority therapeutic target in PD and inhibition of its activity is hypothesized to be beneficial.</p><p><strong>Areas covered: </strong>LRRK2 targeting agents, in particular kinase inhibitors and agents reducing LRRK2 expression show promise in model systems and have progressed to phase I and phase II clinical testing for PD. Several additional targeting strategies for LRRK2 are emerging, based on promoting specific 'healthy' LRRK2 quaternary structures, heteromeric complexes and conformations.</p><p><strong>Expert opinion: </strong>It can be expected that LRRK2 targeting strategies may proceed to phase III clinical testing for PD in the next five years, allowing the field to discover the real clinical value of LRRK2 targeting strategies.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"773-788"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633115","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":"The therapeutic potential of phosphodiesterase 9 (PDE9) inhibitors: a patent review (2018-present).","authors":"Chen Zhang, Zhao-Hang Xue, Wei-Hao Luo, Mei-Yan Jiang, Yinuo Wu","doi":"10.1080/13543776.2024.2376632","DOIUrl":"10.1080/13543776.2024.2376632","url":null,"abstract":"<p><strong>Introduction: </strong>Phosphodiesterase 9 (PDE9) has been demonstrated as a potential target for neurological disorders and cardiovascular diseases, such as Alzheimer's disease and heart failure. For the last few years, a series of PDE9 inhibitors with structural diversities have been developed and patented by researchers and pharmaceutical companies, providing insights into first-in-class therapies of PDE9 drug candidates.</p><p><strong>Area covered: </strong>This review provides an overview of PDE9 inhibitors in patents from 2018 to the present.</p><p><strong>Expert opinion: </strong>Only a few of the current PDE9 inhibitors are highly selective over other PDEs, which limits their application in pharmacological and clinical research. The design and development of highly selective PDE9 inhibitors remain the top priority in future research. The advantages of targeting PDE9 rather than other PDEs in treating neurodegenerative diseases need to be explained thoroughly. Besides, application of PDE9 inhibitor-based combination therapies sheds light on treating diabetes and refractory heart diseases. Finally, PDE9 inhibitors should be further explored in clinical indications beyond neurological disorders and cardiovascular diseases.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"759-772"},"PeriodicalIF":5.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558497","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}
Hidayat Hussain, Daijie Wang, Hesham R El-Seedi, Luay Rashan, Ishtiaq Ahmed, Muzaffar Abbas, Nilufar Z Mamadalieva, Haider N Sultani, Muhammad Iftikhar Hussain, Syed Tasadaque A Shah
{"title":"Therapeutic potential of boswellic acids: an update patent review (2016-2023).","authors":"Hidayat Hussain, Daijie Wang, Hesham R El-Seedi, Luay Rashan, Ishtiaq Ahmed, Muzaffar Abbas, Nilufar Z Mamadalieva, Haider N Sultani, Muhammad Iftikhar Hussain, Syed Tasadaque A Shah","doi":"10.1080/13543776.2024.2369626","DOIUrl":"10.1080/13543776.2024.2369626","url":null,"abstract":"<p><strong>Introduction: </strong>Boswellic acids (BAs) are a group of pentacyclic triterpenoids of the ursane and oleanane type. They have shown very interesting biological properties that have led to the development of a number of synthesis protocols. Both natural BAs and their synthetic derivatives may be useful in the treatment of a variety of cancers, viral infections and inflammatory diseases.</p><p><strong>Areas covered: </strong>This review covers patents relating to the therapeutic activities of natural BAs and their synthetic derivatives. The latest patented studies of boswellic acids (are summarized by using the keywords 'boswellic acid,' in SciFinder, PubMed, and Google Patents and databases in the year from 2016 to 2023.</p><p><strong>Expert opinion: </strong>Boswellic acids have shown potent antiviral, anticancer and anti-inflammatory potential. Few BAs analogues have been prepared by modification at the C24-CO<sub>2</sub>H functional groups. In particular, the C-24 amide and amino analogues have shown enhanced anticancer effects compared to the parent AKBA. In addition, BAs have the ability to form conjugates with other antiviral, anti-inflammatory and anticancer drugs that synergistically enhance their biological efficacy. In addition, this conjugation strategy will increase the solubility and bioavailability of BAs, which is one of the most important issues in the development of BAs.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"723-732"},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534105","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}
Kai Wang, Fen Zhong, Zhou-Dong Zhang, Huan-Qiu Li, Sheng Tian
{"title":"Recent advances in the development of P2Y<sub>14</sub>R inhibitors: a patent and literature review (2018-present).","authors":"Kai Wang, Fen Zhong, Zhou-Dong Zhang, Huan-Qiu Li, Sheng Tian","doi":"10.1080/13543776.2024.2369634","DOIUrl":"10.1080/13543776.2024.2369634","url":null,"abstract":"<p><strong>Introduction: </strong>The P2Y<sub>14</sub> receptor (P2Y<sub>14</sub>R), a member of the G protein-coupled receptor family, is activated by extracellular nucleotides. Due to its involvement in inflammatory, immunological and other associated processes, P2Y<sub>14</sub>R has emerged as a promising therapeutic target. Despite lacking a determined three-dimensional crystal structure, the homology modeling technique based on closely related P2Y receptors' crystallography has been extensively utilized for developing active compounds targeting P2Y<sub>14</sub>R. Recent discoveries have unveiled numerous highly effective and subtype-specific P2Y<sub>14</sub>R inhibitors. This study presents an overview of the latest advancements in P2Y<sub>14</sub>R inhibitors.</p><p><strong>Areas covered: </strong>This review presents an overview of the advancements in P2Y<sub>14</sub>R inhibitor research over the past five years, encompassing new patents, journal articles, and highlighting the therapeutic prospects inherent in these compounds.</p><p><strong>Expert opinion: </strong>The recent revelation of the vast potential of P2Y<sub>14</sub>R inhibitors has led to the development of novel compounds that exhibit promising capabilities for the treatment of sterile inflammation of the kidney, potentially diabetes, and asthma. Despite being a relatively nascent class of compounds, certain members have already exhibited their capacity to surmount specific challenges posed by conventional P2Y<sub>14</sub>R inhibitors. Targeting P2Y<sub>14</sub>R through small molecules may present a promising therapeutic strategy for effectively managing diverse inflammatory diseases.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"611-625"},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418557","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}
Miroslav Kosar, Leonard Mach, Erick M Carreira, Marc Nazaré, Pal Pacher, Uwe Grether
{"title":"Patent review of cannabinoid receptor type 2 (CB<sub>2</sub>R) modulators (2016-present).","authors":"Miroslav Kosar, Leonard Mach, Erick M Carreira, Marc Nazaré, Pal Pacher, Uwe Grether","doi":"10.1080/13543776.2024.2368745","DOIUrl":"10.1080/13543776.2024.2368745","url":null,"abstract":"<p><strong>Introduction: </strong>Cannabinoid receptor type 2 (CB<sub>2</sub>R), predominantly expressed in immune tissues, is believed to play a crucial role within the body's protective mechanisms. Its modulation holds immense therapeutic promise for addressing a wide spectrum of dysbiotic conditions, including cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, and autoimmune diseases, as well as lung disorders, cancer, and pain management.</p><p><strong>Areas covered: </strong>This review is an account of patents from 2016 up to 2023 which describes novel CB<sub>2</sub>R ligands, therapeutic applications, synthesis, as well as formulations of CB<sub>2</sub>R modulators.</p><p><strong>Expert opinion: </strong>The patents cover a vast, structurally diverse chemical space. The focus of CB<sub>2</sub>R ligand development has shifted from unselective dual-cannabinoid receptor type 1 (CB<sub>1</sub>R) and 2 agonists toward agonists with high selectivity over CB<sub>1</sub>R, particularly for indications associated with inflammation and tissue injury. Currently, there are at least eight CB<sub>2</sub>R agonists and one antagonist in active clinical development. A better understanding of the endocannabinoid system (ECS) and in particular of CB<sub>2</sub>R pharmacology is required to unlock the receptor's full therapeutic potential.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"665-700"},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418556","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":"Inhibition of GTPase KRAS<sup>G12D</sup>: a review of patent literature.","authors":"Yuhang Li, Le Yang, Xiaoran Li, Xiaojin Zhang","doi":"10.1080/13543776.2024.2369630","DOIUrl":"10.1080/13543776.2024.2369630","url":null,"abstract":"<p><strong>Introduction: </strong>KRAS is a critical oncogenic protein intricately involved in tumor progression, and the difficulty in targeting KRAS has led it to be classified as an 'undruggable target.' Among the various KRAS mutations, KRAS<sup>G12D</sup> is highly prevalent and represents a promising therapeutic target, yet there are currently no approved inhibitors for it.</p><p><strong>Area covered: </strong>This review summarizes numerous patents and literature featuring inhibitors or degraders of KRAS<sup>G12D</sup> through searching relevant information in PubMed, SciFinder and Web of Science databases from 2021 to February 2024, providing an overview of the research progress on inhibiting KRAS<sup>G12D</sup> in terms of design strategies, chemical structures, biological activities, and clinical advancements.</p><p><strong>Expert opinion: </strong>Since the approval of <b>AMG510</b> (Sotorasib), there has been an increasing focus on the inhibition of KRAS<sup>G12D</sup>, leading to numerous reports of related inhibitors and degraders. Among them, <b>MRTX1133</b>, as the first KRAS<sup>G12D</sup> inhibitor to enter clinical trials, has demonstrated excellent tumor suppression in various KRAS<sup>G12D</sup>-bearing human tumor xenograft models. It is important to note, however, that understanding the mechanisms of acquired resistance caused by KRAS inhibition and developing additional combination therapies is crucial. Moreover, seeking covalent inhibition of KRAS<sup>G12D</sup> also holds significant potential.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"701-721"},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330732","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":"FAK inhibitors in cancer, a patent review - an update on progress.","authors":"Ya-Xi Ye, Yu-Yao Cao, Li-Sheng Xu, Hai-Chao Wang, Xin-Hua Liu, Hai-Liang Zhu","doi":"10.1080/13543776.2024.2368742","DOIUrl":"10.1080/13543776.2024.2368742","url":null,"abstract":"<p><strong>Introduction: </strong>Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation.</p><p><strong>Areas covered: </strong>There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research.</p><p><strong>Expert opinion: </strong>FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.</p>","PeriodicalId":12314,"journal":{"name":"Expert Opinion on Therapeutic Patents","volume":" ","pages":"593-610"},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467286","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}