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An updated patent review of TRPA1 antagonists (2020 - present). TRPA1 拮抗剂的最新专利回顾(2020 年至今)。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-01 Epub Date: 2024-06-17 DOI: 10.1080/13543776.2024.2364798
Rosa Maria Vitale, Luciano de Petrocellis, Pietro Amodeo

Introduction: TRPA1 is a nonselective calcium channel, a member of the transient receptor potential (TRP) superfamily, also referred to as the 'irritant' receptor, being activated by pungent and noxious exogenous chemicals as well as by endogenous algogenic stimuli, to elicit pain, itching, and inflammatory conditions. For this reason, it is considered an attractive therapeutic target to treat a wide range of diseases including acute and chronic pain, itching, and inflammatory airway diseases.

Areas covered: The present review covers patents on TRPA1 antagonists disclosed from 2020 to present, falling in the following main classes: i) novel therapeutic applications for known or already disclosed antagonists, ii) identification and characterization of TRPA1 antagonists from natural sources, and iii) synthesis and evaluation of novel compounds.

Expert opinion: Despite the limited number of TRPA1 antagonists in clinical trials, there is an ever-growing interest on this receptor-channel as therapeutic target, mainly due to the relevant outcomes from basic research, which unveiled novel physio-pathological mechanisms where TRPA1 is believed to play a pivotal role, for example the Alzheimer's disease or ocular diseases, expanding the panel of potential therapeutic applications for TRPA1 modulators.

简介TRPA1 是一种非选择性钙通道,属于瞬时受体电位(TRP)超家族,也被称为 "刺激性 "受体,可被刺激性和有害的外源性化学物质以及内源性藻类刺激激活,从而引发疼痛、瘙痒和炎症。因此,它被认为是治疗各种疾病(包括急性和慢性疼痛、瘙痒和气道炎症性疾病)的有吸引力的治疗靶点:本综述涵盖 2020 年至今公开的 TRPA1 拮抗剂专利,主要分为以下几类:i) 已知或已公开拮抗剂的新型治疗应用;ii) 天然 TRPA1 拮抗剂的鉴定和表征;iii) 新型化合物的合成和评估:尽管临床试验中的 TRPA1 拮抗剂数量有限,但人们对这一受体通道作为治疗靶点的兴趣与日俱增,这主要归功于基础研究的相关成果,这些成果揭示了新的生理病理机制,据信 TRPA1 在其中发挥着关键作用,例如阿尔茨海默病或眼部疾病,从而扩大了 TRPA1 调节剂的潜在治疗应用范围。
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引用次数: 0
PIM kinase inhibitors: an updated patent review (2016-present). PIM 激酶抑制剂:最新专利回顾(2016 年至今)。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-01 Epub Date: 2024-06-13 DOI: 10.1080/13543776.2024.2365411
Anushka Sharma, Rahul Dubey, Shankar Gupta, Vivek Asati, Vipul Kumar, Dileep Kumar, Debarshi Kar Mahapatra, Meenakshi Jaiswal, Sanmati Kumar Jain, Sanjay Kumar Bharti

Introduction: PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer.

Areas covered: A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted.

Expert opinion: Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.

简介:PIM 激酶(PIM-1、PIM-2 和 PIM-3据报道,PIM 激酶(PIM-1、PIM-2 和 PIM-3)在控制细胞存活、增殖和分化的信号级联中发挥着至关重要的作用。这些激酶的过度表达会导致血液恶性肿瘤,如弥漫性大 B 细胞淋巴瘤(DLBCL)、多发性骨髓瘤、白血病、淋巴瘤和前列腺癌等。PIM 激酶作为生物标志物和潜在的治疗靶点,有望实现癌症的精准治疗。选择性 PIM-1、PIM-2 和/或 PIM-3 异构体抑制剂已在晚期癌症患者(包括复发/难治性癌症患者)中显示出显著疗效:全面回顾了PIM激酶(PIM-1、PIM-2和PIM-3)在肿瘤发生中的作用,重点介绍了PIM激酶专利抑制剂(2016年至今)及其药理学和结构见解:最近,作为治疗靶点的PIM激酶,即PIM-1、PIM-2和PIM-3(丝氨酸/苏氨酸蛋白激酶家族成员)在肿瘤学领域,尤其是血液恶性肿瘤领域引起了极大的兴趣。三唑并吡啶、吡唑并吡啶、咪唑并哒嗪、噁二唑硫酮、吡唑并嘧啶、三唑并哒嗪、咪唑并哒嗪、吡唑并喹唑啉和吡唑并吡啶等。在癌症化疗中显示出良好的效果。
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引用次数: 0
A patent review of SHP2 allosteric inhibitors (2018-present). SHP2异构抑制剂专利回顾(2018年至今)。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-01 Epub Date: 2024-06-13 DOI: 10.1080/13543776.2024.2365410
Alessia Petrocchi, Alina Ciammaichella

Introduction: SHP2 (Src homology region 2-containing protein tyrosine phosphatase 2) is a target of interest for cancer therapy due to its key role in the regulation of the RAS/MAPK signal transduction pathway downstream of Receptor Tyrosine Kinases (RTKs). Moreover, SHP2 can inhibit T cells via the PD-1/PD-L1 pathway. SHP2 plays a critical role in numerous physiological and pathological cellular processes, such as cell proliferation, survival, and migration.

Areas covered: This review examines SHP2 allosteric inhibitors reported in patents published in Espacenet and Scifinder databases from 2018 to present. An overview of claimed structures is conducted, focusing attention on structural modifications compared to SHP099, the first described allosteric inhibitor of SHP2.

Expert opinion: Multiple potent allosteric SHP2 inhibitors have been discovered, disclosed, and tested in a variety of preclinical cancer models with strong evidence of efficacy. Fifteen compounds are currently in clinical development, but none of them have been approved for marketing. Until now, long-term benefit of SHP2 inhibitors as monotherapy agents have not been demonstrated due to acquired mechanisms of resistance and/or lack of efficacy. However, combination therapies with a variety of agents, such as MEK, BRAF, EGFR, RAS-G12C and PDL-1 inhibitors, have high potential and are currently an extensive area of investigation.

导言:SHP2(含Src同源区2的蛋白酪氨酸磷酸酶2)在受体酪氨酸激酶(RTK)下游的RAS/MAPK信号转导通路的调控中起着关键作用,因此是癌症治疗的一个受关注的靶点。此外,SHP2 还能通过 PD-1/PD-L1 通路抑制 T 细胞。SHP2 在细胞增殖、存活和迁移等众多生理和病理过程中发挥着关键作用:本综述研究了 2018 年至今在 Espacenet 和 Scifinder 数据库中公布的专利中报告的 SHP2 异生抑制剂。综述了权利要求结构,重点关注与SHP099(首个描述的SHP2异构抑制剂)相比的结构修饰:多种强效的SHP2异构抑制剂已被发现、公开,并在多种临床前癌症模型中进行了测试,其疗效证据确凿。目前有 15 种化合物处于临床开发阶段,但没有一种获准上市。迄今为止,由于获得性耐药机制和/或缺乏疗效,SHP2 抑制剂作为单一疗法药物的长期益处尚未得到证实。不过,与 MEK、BRAF、表皮生长因子受体、RAS-G12C 和 PDL-1 抑制剂等多种药物的联合疗法潜力巨大,目前是一个广泛的研究领域。
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引用次数: 0
Biomedical applications of prokaryotic carbonic anhydrases: an update. 原核碳酸酐酶的生物医学应用:最新进展。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-05-01 Epub Date: 2024-06-11 DOI: 10.1080/13543776.2024.2365407
Clemente Capasso, Claudiu T Supuran

Introduction: This review offers an updated perspective on the biomedical applications of prokaryotic carbonic anhydrases (CAs), emphasizing their potential as targets for drug development against antibiotic-resistant bacterial infections. A systematic review of literature from PubMed, Web of Science, and Google Scholar has been conducted to provide a comprehensive analysis.

Area covered: It delves into the pivotal roles of prokaryotic CAs in bacterial metabolism and their distinctions from mammalian CAs. The review explores the diversity of CA classes in bacteria, discusses selective inhibitors targeting bacterial CAs, and explores their potential applications in biomedical research. Furthermore, it analyzes clinical trials investigating the efficacy of carbonic anhydrase inhibitors (CAIs) and patented approaches for developing antibacterial CAIs, highlighting their translational potential in creating innovative antibacterial agents.

Expert opinion: Recent years have witnessed increased recognition of CA inhibition as a promising strategy against bacterial infections. Challenges persist in achieving selectivity over human isoforms and optimizing therapeutic efficacy. Structural biology techniques provide insights into unique active site architectures, guiding selective inhibitor design. The review underscores the importance of interdisciplinary collaborations, innovative drug delivery systems, and advanced drug discovery approaches in unlocking the full therapeutic potential of prokaryotic CA inhibitors. It emphasizes the significance of these efforts in addressing antibiotic resistance and improving patient outcomes.

导言:这篇综述提供了原核生物碳酸酐酶(CAs)生物医学应用的最新视角,强调了它们作为抗生素耐药细菌感染药物开发靶点的潜力。为了提供全面的分析,我们对来自 PubMed、Web of Science 和 Google Scholar 的文献进行了系统综述:该综述深入探讨了原核 CA 在细菌新陈代谢中的关键作用及其与哺乳动物 CA 的区别。综述探讨了细菌中 CA 种类的多样性,讨论了针对细菌 CA 的选择性抑制剂,并探讨了它们在生物医学研究中的潜在应用。此外,它还分析了研究碳酸酐酶抑制剂(CAIs)疗效的临床试验以及开发抗菌 CAIs 的专利方法,强调了它们在创造创新抗菌剂方面的转化潜力:近年来,人们越来越认识到CA抑制剂是一种很有前景的抗细菌感染策略。在实现对人类同工酶的选择性和优化疗效方面,挑战依然存在。结构生物学技术提供了对独特活性位点结构的见解,为选择性抑制剂的设计提供了指导。这篇综述强调了跨学科合作、创新给药系统和先进药物发现方法在充分挖掘原核 CA 抑制剂治疗潜力方面的重要性。它强调了这些努力在解决抗生素耐药性和改善患者预后方面的重要意义。
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引用次数: 0
Targeting the TGF-β signaling pathway: an updated patent review (2021–present) 靶向 TGF-β 信号通路:最新专利回顾(2021 年至今)
IF 6.6 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-22 DOI: 10.1080/13543776.2024.2346325
Wenhao Guo, Hanwen Liu, Yong Yan, Di Wu, Hequan Yao, Kejiang Lin, Xuanyi Li
The TGF-β signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This rev...
TGF-β 信号通路是一个复杂的网络,在调节基本生物功能方面发挥着至关重要的作用,并与多种疾病的发生和发展有关。本研究的目的是对TGF-β信号通路的研究。
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引用次数: 0
PCSK9 inhibitors: a patent review 2018-2023 PCSK9 抑制剂:2018-2023 年专利回顾
IF 6.6 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-08 DOI: 10.1080/13543776.2024.2340569
Enrico Mario Alessandro Fassi, Andrea Citarella, Marco Albani, Erica Ginevra Milano, Laura Legnani, Carmen Lammi, Alessandra Silvani, Giovanni Grazioso
Published in Expert Opinion on Therapeutic Patents (Just accepted, 2024)
发表于《关于治疗专利的专家意见》(刚刚接受,2024 年)
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引用次数: 0
Biofilm and bacterial membrane vesicles: recent advances 生物膜和细菌膜囊:最新进展
IF 6.6 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-05 DOI: 10.1080/13543776.2024.2338101
Valentina Puca, Beatrice Marinacci, Benedetta Pellegrini, Floriana Campanile, Maria Santagati, Rossella Grande
Bacterial Membrane Vesicles (MVs) play important roles in cell-to-cell communication and transport of several molecules. Such structures are essential components of Extracellular Polymeric Substanc...
细菌膜泡(MVs)在细胞间通信和多种分子运输中发挥着重要作用。这种结构是细胞外聚合物基质的重要组成部分。
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引用次数: 0
Synthetic lethality: targeting SMARCA2 ATPase in SMARCA4-deficient tumors – a review of patent literature from 2019–30 June 2023 合成致死:在SMARCA4缺陷肿瘤中靶向SMARCA2 ATP酶--2019年至2023年6月30日专利文献综述
IF 6.6 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-05 DOI: 10.1080/13543776.2024.2338111
Kyle D. Reichl, Esther C. Y. Lee, Ariamala Gopalsamy
The multi-subunit SWI/SNF chromatin remodeling complex is a key epigenetic regulator for many cellular processes, and several subunits are found to be mutated in human cancers. The inactivating mut...
多亚基SWI/SNF染色质重塑复合体是许多细胞过程的关键表观遗传调节因子,在人类癌症中发现有几个亚基发生了突变。失活突变...
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引用次数: 0
An overview on recent patents and technologies on nanoparticles for nucleic acid delivery 核酸递送纳米粒子最新专利和技术概览
IF 6.6 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-05 DOI: 10.1080/13543776.2024.2338097
Larissa Moraes dos Santos Fonseca, Bruna Aparecida Souza Machado, Fabricia Oliveira Oliveira, Jânio Rodrigo de Jesus Santos, Jaqueline Wang da Silva, Katharine Valeria Saraiva Hodel, Brisa Gonçalves Rosatti, Claudio Damasceno Pinto, Milena Botelho Pereira Soares
Nucleic acid-based therapeutics offer groundbreaking potential for treating genetic diseases and advancing next-generation vaccines. Despite their promise, challenges in efficient delivery persist ...
基于核酸的疗法为治疗遗传疾病和促进下一代疫苗的发展提供了突破性的潜力。尽管核酸疗法大有可为,但在高效传递方面仍存在挑战......
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引用次数: 0
Targeting the relaxin-3/RXFP3 system: a patent review for the last two decades 以松弛素-3/RXFP3 系统为靶标:过去二十年的专利回顾
IF 6.6 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2024-04-04 DOI: 10.1080/13543776.2024.2338099
Md Toufiqur Rahman, Hetti Handi Chaminda Lakmal, Javeena Hussain, Chunyang Jin
The neuropeptide relaxin-3/RXFP3 system belongs to the relaxin/insulin superfamily and is involved in many important physiological processes, such as stress responses, appetite control, and motivat...
神经肽弛缓素-3/RXFP3系统属于弛缓素/胰岛素超家族,参与许多重要的生理过程,如应激反应、食欲控制和激励。
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引用次数: 0
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Expert Opinion on Therapeutic Patents
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