Introduction: Owing to limited efficient treatment strategies for highly prevalent and distressing Parkinson's disease (PD), an impending need emerged for deciphering new modes and mechanisms for effective management. SH-SY5Y-based in vitro neuronal models have emerged as a new possibility for the elucidation of cellular and molecular processes in the pathogenesis of PD. SH-SY5Y cells are of human origin, adhered to catecholaminergic neuronal attributes, which consequences in imparting wide acceptance and significance to this model over conventional in vitro PD models for high-throughput screening of therapeutics.
Areas covered: Herein, the authors review the SH-SY5Y cell line and its value to PD research. The authors also provide the reader with their expert perspectives on how these developments can lead to the development of new impactful therapeutics.
Expert opinion: Encouraged by recent research on SH-SY5Y cell lines, it was envisaged that this in vitro model can serve as a primary model for assessing efficacy and toxicity of new therapeutics as well as for nanocarriers' capacity in delivering therapeutic agents across BBB. Considering the proximity with human neuronal environment as in pathogenic PD conditions, SH-SY5Y cell lines vindicated consistency and reproducibility in experimental results. Accordingly, exploitation of this standardized SH-SY5Y cell line can fast-track the drug discovery and development path for novel therapeutics.
{"title":"The SH-SY5Y cell line: a valuable tool for Parkinson's disease drug discovery.","authors":"Manisha Pandey, Varnita Karmakar, Ankit Majie, Monika Dwivedi, Shadab Md, Bapi Gorain","doi":"10.1080/17460441.2023.2293158","DOIUrl":"10.1080/17460441.2023.2293158","url":null,"abstract":"<p><strong>Introduction: </strong>Owing to limited efficient treatment strategies for highly prevalent and distressing Parkinson's disease (PD), an impending need emerged for deciphering new modes and mechanisms for effective management. SH-SY5Y-based <i>in vitro</i> neuronal models have emerged as a new possibility for the elucidation of cellular and molecular processes in the pathogenesis of PD. SH-SY5Y cells are of human origin, adhered to catecholaminergic neuronal attributes, which consequences in imparting wide acceptance and significance to this model over conventional <i>in vitro</i> PD models for high-throughput screening of therapeutics.</p><p><strong>Areas covered: </strong>Herein, the authors review the SH-SY5Y cell line and its value to PD research. The authors also provide the reader with their expert perspectives on how these developments can lead to the development of new impactful therapeutics.</p><p><strong>Expert opinion: </strong>Encouraged by recent research on SH-SY5Y cell lines, it was envisaged that this <i>in vitro</i> model can serve as a primary model for assessing efficacy and toxicity of new therapeutics as well as for nanocarriers' capacity in delivering therapeutic agents across BBB. Considering the proximity with human neuronal environment as in pathogenic PD conditions, SH-SY5Y cell lines vindicated consistency and reproducibility in experimental results. Accordingly, exploitation of this standardized SH-SY5Y cell line can fast-track the drug discovery and development path for novel therapeutics.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794687","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}
Pub Date : 2024-03-01Epub Date: 2023-12-25DOI: 10.1080/17460441.2023.2294118
Maria Dichiara, Giuseppe Cosentino, Giorgia Giordano, Lorella Pasquinucci, Agostino Marrazzo, Giuliana Costanzo, Emanuele Amata
Introduction: With the increasing incidence and prevalence of neurological disorders globally, there is a paramount need for new pharmacotherapies. BBB effectively protects the brain but raises a profound challenge to drug permeation, with less than 2% of most drugs reaching the CNS.
Areas covered: This article reviews aspects of the most recent design strategies, providing insights into ideas and concepts in CNS drug discovery. An overview of the products available on the market is given and why clinical trials are continuously failing is discussed.
Expert opinion: Among the available CNS drugs, small molecules account for most successful CNS therapeutics due to their ability to penetrate the BBB through passive or carrier-mediated mechanisms. The development of new CNS drugs is very difficult. To date, there is a lack of effective drugs for alleviating or even reversing the progression of brain diseases. Particularly, the use of artificial intelligence strategies, together with more appropriate animal models, may enable the design of molecules with appropriate permeation, to elicit a biological response from the neurotherapeutic target.
{"title":"Designing drugs optimized for both blood-brain barrier permeation and intra-cerebral partition.","authors":"Maria Dichiara, Giuseppe Cosentino, Giorgia Giordano, Lorella Pasquinucci, Agostino Marrazzo, Giuliana Costanzo, Emanuele Amata","doi":"10.1080/17460441.2023.2294118","DOIUrl":"10.1080/17460441.2023.2294118","url":null,"abstract":"<p><strong>Introduction: </strong>With the increasing incidence and prevalence of neurological disorders globally, there is a paramount need for new pharmacotherapies. BBB effectively protects the brain but raises a profound challenge to drug permeation, with less than 2% of most drugs reaching the CNS.</p><p><strong>Areas covered: </strong>This article reviews aspects of the most recent design strategies, providing insights into ideas and concepts in CNS drug discovery. An overview of the products available on the market is given and why clinical trials are continuously failing is discussed.</p><p><strong>Expert opinion: </strong>Among the available CNS drugs, small molecules account for most successful CNS therapeutics due to their ability to penetrate the BBB through passive or carrier-mediated mechanisms. The development of new CNS drugs is very difficult. To date, there is a lack of effective drugs for alleviating or even reversing the progression of brain diseases. Particularly, the use of artificial intelligence strategies, together with more appropriate animal models, may enable the design of molecules with appropriate permeation, to elicit a biological response from the neurotherapeutic target.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032216","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}
Pub Date : 2024-03-01Epub Date: 2024-01-23DOI: 10.1080/17460441.2024.2305730
Samima Khatun, Sk Abdul Amin, Debasmita Choudhury, Boby Chowdhury, Tarun Jha, Shovanlal Gayen
Introduction: HIV-infected cells may rebound due to the existence of the silent HIV-infected memory CD4+ T cells (HIV latency). This HIV latency makes the disease almost incurable. In latency, the integrated proviral DNA of HIV is transcriptionally silenced partly due to the activity of histone deacetylases (HDACs). Hence, inhibition of HDAC is considered a prime target for HIV latency reversal.
Areas covered: A brief biology and function of HDACs have been discussed to identify key points to design HDAC inhibitors (HDACis). This article summarizes recent achievements in the development of HDACis to achieve HIV latency reversal. Structure-activity relationships (SARs) of some series of compounds were also explored.
Expert opinion: Depletion of the HIV reservoir is the only way to end this deadly epidemic. HDACis are latency-reversing agents (LRA) that can be used to 'shock' the latently infected CD4+ T cells to induce them to produce viral proteins. It is interesting to note that HDAC3, which is extensively expressed in resting T cells, is specifically preferred by benzamide-containing HDACis for inhibition. Thus, the benzamide class of compounds should be explored. Nevertheless, more data on selective HDAC inhibition is needed for further development of HDACis in HIV latency reversal.
导言:由于存在沉默的艾滋病毒感染记忆 CD4+ T 细胞(艾滋病毒潜伏期),艾滋病毒感染细胞可能会反弹。这种艾滋病病毒潜伏期使这种疾病几乎无法治愈。在潜伏期,HIV 的整合前病毒 DNA 在转录上处于沉默状态,部分原因是组蛋白去乙酰化酶(HDAC)的活性。因此,抑制 HDAC 被认为是逆转 HIV 潜伏期的主要目标:本文简要讨论了 HDAC 的生物学特性和功能,以确定设计 HDAC 抑制剂(HDACis)的关键点。本文总结了最近在开发HDACis以逆转HIV潜伏期方面取得的成就。同时还探讨了一些系列化合物的结构-活性关系(SARs):耗尽艾滋病病毒库是结束这一致命流行病的唯一途径。HDACis 是一种潜伏逆转剂 (LRA),可用于 "冲击 "潜伏感染的 CD4+ T 细胞,诱导它们产生病毒蛋白。值得注意的是,静息 T 细胞中广泛表达的 HDAC3 特别容易被含苯甲酰胺的 HDACis 抑制。因此,应探索苯甲酰胺类化合物。不过,还需要更多关于选择性 HDAC 抑制的数据,以进一步开发用于逆转 HIV 潜伏期的 HDACis。
{"title":"Advances in structure-activity relationships of HDAC inhibitors as HIV latency-reversing agents.","authors":"Samima Khatun, Sk Abdul Amin, Debasmita Choudhury, Boby Chowdhury, Tarun Jha, Shovanlal Gayen","doi":"10.1080/17460441.2024.2305730","DOIUrl":"10.1080/17460441.2024.2305730","url":null,"abstract":"<p><strong>Introduction: </strong>HIV-infected cells may rebound due to the existence of the silent HIV-infected memory CD4+ T cells (HIV latency). This HIV latency makes the disease almost incurable. In latency, the integrated proviral DNA of HIV is transcriptionally silenced partly due to the activity of histone deacetylases (HDACs). Hence, inhibition of HDAC is considered a prime target for HIV latency reversal.</p><p><strong>Areas covered: </strong>A brief biology and function of HDACs have been discussed to identify key points to design HDAC inhibitors (HDACis). This article summarizes recent achievements in the development of HDACis to achieve HIV latency reversal. Structure-activity relationships (SARs) of some series of compounds were also explored.</p><p><strong>Expert opinion: </strong>Depletion of the HIV reservoir is the only way to end this deadly epidemic. HDACis are latency-reversing agents (LRA) that can be used to 'shock' the latently infected CD4+ T cells to induce them to produce viral proteins. It is interesting to note that HDAC3, which is extensively expressed in resting T cells, is specifically preferred by benzamide-containing HDACis for inhibition. Thus, the benzamide class of compounds should be explored. Nevertheless, more data on selective HDAC inhibition is needed for further development of HDACis in HIV latency reversal.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519981","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}
Pub Date : 2024-03-01Epub Date: 2023-12-20DOI: 10.1080/17460441.2023.2294947
Chloe P Whitworth, William J Polacheck
Introduction: Vascular diseases impart a tremendous burden on healthcare systems in the United States and across the world. Efforts to improve therapeutic interventions are hindered by limitations of current experimental models. The integration of patient-derived cells with organ-on-chip (OoC) technology is a promising avenue for preclinical drug screening that improves upon traditional cell culture and animal models.
Areas covered: The authors review induced pluripotent stem cells (iPSC) and blood outgrowth endothelial cells (BOEC) as two sources for patient-derived endothelial cells (EC). They summarize several studies that leverage patient-derived EC and OoC for precision disease modeling of the vasculature, with a focus on applications for drug discovery. They also highlight the utility of patient-derived EC in other translational endeavors, including ex vivo organogenesis and multi-organ-chip integration.
Expert opinion: Precision disease modeling continues to mature in the academic space, but end-use by pharmaceutical companies is currently limited. To fully realize their transformative potential, OoC systems must balance their complexity with their ability to integrate with the highly standardized and high-throughput experimentation required for drug discovery and development.
{"title":"Vascular organs-on-chip made with patient-derived endothelial cells: technologies to transform drug discovery and disease modeling.","authors":"Chloe P Whitworth, William J Polacheck","doi":"10.1080/17460441.2023.2294947","DOIUrl":"10.1080/17460441.2023.2294947","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular diseases impart a tremendous burden on healthcare systems in the United States and across the world. Efforts to improve therapeutic interventions are hindered by limitations of current experimental models. The integration of patient-derived cells with organ-on-chip (OoC) technology is a promising avenue for preclinical drug screening that improves upon traditional cell culture and animal models.</p><p><strong>Areas covered: </strong>The authors review induced pluripotent stem cells (iPSC) and blood outgrowth endothelial cells (BOEC) as two sources for patient-derived endothelial cells (EC). They summarize several studies that leverage patient-derived EC and OoC for precision disease modeling of the vasculature, with a focus on applications for drug discovery. They also highlight the utility of patient-derived EC in other translational endeavors, including ex vivo organogenesis and multi-organ-chip integration.</p><p><strong>Expert opinion: </strong>Precision disease modeling continues to mature in the academic space, but end-use by pharmaceutical companies is currently limited. To fully realize their transformative potential, OoC systems must balance their complexity with their ability to integrate with the highly standardized and high-throughput experimentation required for drug discovery and development.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10922379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794891","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}
Pub Date : 2024-03-01Epub Date: 2023-12-11DOI: 10.1080/17460441.2023.2293157
Wenqiang Cui, Shuguang Yuan
{"title":"Will the hype of automated drug discovery finally be realized?","authors":"Wenqiang Cui, Shuguang Yuan","doi":"10.1080/17460441.2023.2293157","DOIUrl":"10.1080/17460441.2023.2293157","url":null,"abstract":"","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794892","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}
Pub Date : 2024-03-01Epub Date: 2024-01-18DOI: 10.1080/17460441.2024.2305735
Erica Benedetti, Laurent Micouin
{"title":"Have spirocyclic scaffolds been properly utilized in recent drug discovery efforts?","authors":"Erica Benedetti, Laurent Micouin","doi":"10.1080/17460441.2024.2305735","DOIUrl":"10.1080/17460441.2024.2305735","url":null,"abstract":"","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471699","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}
Pub Date : 2024-02-01DOI: 10.1080/17460441.2023.2284201
You-Cai Xiao, Fen-Er Chen
Introduction: Vinyl sulfones are a special sulfur-containing structural unit that have attracted considerable attention, owing to their important role in serving as key structural motifs of various biologically active compounds as well as serving as versatile building blocks for organic transformations. The synthetic strategy of vinyl sulfone derivatives has been substantially upgraded over the past 30 years, and the wide application of this functional group in drug design and discovery has been promoted.
Area covered: In this review, the authors review the application of vinyl sulfones in drug discovery and select optimized compounds which might have significant impact or potential inspiration for drug design.
Expert opinion: Vinyl sulfones have been reported to target various macromolecular targets via non-covalent or covalent interactions, including multiple kinases, tubulin, cysteine protease, transcription factor, and so on. Thus, it has been significantly applied as a privileged scaffold in the design of anticancer, anti-infective, anti-inflammatory, and neuroprotective agents. However, much work remains to be done to improve the drug-like properties, such as chemical and metabolic stability, ADME, and toxicity. Besides, the chemical space of vinyl sulfones needs to be expanded, including but not limited to the design of constrained endocyclic and exocyclic vinyl sulfones.
{"title":"The vinyl sulfone motif as a structural unit for novel drug design and discovery.","authors":"You-Cai Xiao, Fen-Er Chen","doi":"10.1080/17460441.2023.2284201","DOIUrl":"10.1080/17460441.2023.2284201","url":null,"abstract":"<p><strong>Introduction: </strong>Vinyl sulfones are a special sulfur-containing structural unit that have attracted considerable attention, owing to their important role in serving as key structural motifs of various biologically active compounds as well as serving as versatile building blocks for organic transformations. The synthetic strategy of vinyl sulfone derivatives has been substantially upgraded over the past 30 years, and the wide application of this functional group in drug design and discovery has been promoted.</p><p><strong>Area covered: </strong>In this review, the authors review the application of vinyl sulfones in drug discovery and select optimized compounds which might have significant impact or potential inspiration for drug design.</p><p><strong>Expert opinion: </strong>Vinyl sulfones have been reported to target various macromolecular targets via non-covalent or covalent interactions, including multiple kinases, tubulin, cysteine protease, transcription factor, and so on. Thus, it has been significantly applied as a privileged scaffold in the design of anticancer, anti-infective, anti-inflammatory, and neuroprotective agents. However, much work remains to be done to improve the drug-like properties, such as chemical and metabolic stability, ADME, and toxicity. Besides, the chemical space of vinyl sulfones needs to be expanded, including but not limited to the design of constrained endocyclic and exocyclic vinyl sulfones.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397117","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}
Pub Date : 2024-02-01DOI: 10.1080/17460441.2023.2270902
Eoin C O'Connor, Kumiko Kambara, Daniel Bertrand
Introduction: Introduced about 50 years ago, the model of Xenopus oocytes for the expression of recombinant proteins has gained a broad spectrum of applications. The authors herein review the benefits brought from using this model system, with a focus on modeling neurological disease mechanisms and application to drug discovery.
Areas covered: Using multiple examples spanning from ligand gated ion channels to transporters, this review presents, in the light of the latest publications, the benefits offered from using Xenopus oocytes. Studies range from the characterization of gene mutations to the discovery of novel treatments for disorders of the central nervous system (CNS).
Expert opinion: Development of new drugs targeting CNS disorders has been marked by failures in the translation from preclinical to clinical studies. As progress in genetics and molecular biology highlights large functional differences arising from a single to a few amino acid exchanges, the need for drug screening and functional testing against human proteins is increasing. The use of Xenopus oocytes to enable precise modeling and characterization of clinically relevant genetic variants constitutes a powerful model system that can be used to inform various aspects of CNS drug discovery and development.
{"title":"Advancements in the use of xenopus oocytes for modelling neurological disease for novel drug discovery.","authors":"Eoin C O'Connor, Kumiko Kambara, Daniel Bertrand","doi":"10.1080/17460441.2023.2270902","DOIUrl":"10.1080/17460441.2023.2270902","url":null,"abstract":"<p><strong>Introduction: </strong>Introduced about 50 years ago, the model of Xenopus oocytes for the expression of recombinant proteins has gained a broad spectrum of applications. The authors herein review the benefits brought from using this model system, with a focus on modeling neurological disease mechanisms and application to drug discovery.</p><p><strong>Areas covered: </strong>Using multiple examples spanning from ligand gated ion channels to transporters, this review presents, in the light of the latest publications, the benefits offered from using Xenopus oocytes. Studies range from the characterization of gene mutations to the discovery of novel treatments for disorders of the central nervous system (CNS).</p><p><strong>Expert opinion: </strong>Development of new drugs targeting CNS disorders has been marked by failures in the translation from preclinical to clinical studies. As progress in genetics and molecular biology highlights large functional differences arising from a single to a few amino acid exchanges, the need for drug screening and functional testing against human proteins is increasing. The use of Xenopus oocytes to enable precise modeling and characterization of clinically relevant genetic variants constitutes a powerful model system that can be used to inform various aspects of CNS drug discovery and development.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233724","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}
Pub Date : 2024-02-01DOI: 10.1080/17460441.2023.2275640
David R Janero
Introduction: Escalating costs and inherent uncertainties associated with drug discovery invite initiatives to improve its efficiency and de-risk campaigns for inventing better therapeutics. One such initiative involves recognizing and exploiting current approaches in therapeutics invention with molecular mechanisms of action that hold promise for designing and targeting new chemical entities as drugs.
Areas covered: This perspective considers the current contextual framework around three drug-discovery approaches and evaluates their potential to help identify new targets/modalities in small-molecule molecular pharmacology: diversifying ligand-directed phenotypes for G protein-coupled receptor (GPCR) pharmacotherapeutic signaling; developing therapeutic-protein degraders and stabilizers for proximity-inducing pharmacology; and mining organelle biology for druggable therapeutic targets.
Expert opinion: The contemporary drug-discovery approaches examined appear generalizable and versatile to have applications in therapeutics invention beyond those case studies discussed herein. Accordingly, they may be considered strategic trends worthy of note in advancing the field toward novel ways of addressing pharmacotherapeutically unmet medical needs.
{"title":"Current strategic trends in drug discovery: the present as prologue.","authors":"David R Janero","doi":"10.1080/17460441.2023.2275640","DOIUrl":"10.1080/17460441.2023.2275640","url":null,"abstract":"<p><strong>Introduction: </strong>Escalating costs and inherent uncertainties associated with drug discovery invite initiatives to improve its efficiency and de-risk campaigns for inventing better therapeutics. One such initiative involves recognizing and exploiting current approaches in therapeutics invention with molecular mechanisms of action that hold promise for designing and targeting new chemical entities as drugs.</p><p><strong>Areas covered: </strong>This perspective considers the current contextual framework around three drug-discovery approaches and evaluates their potential to help identify new targets/modalities in small-molecule molecular pharmacology: diversifying ligand-directed phenotypes for G protein-coupled receptor (GPCR) pharmacotherapeutic signaling; developing therapeutic-protein degraders and stabilizers for proximity-inducing pharmacology; and mining organelle biology for druggable therapeutic targets.</p><p><strong>Expert opinion: </strong>The contemporary drug-discovery approaches examined appear generalizable and versatile to have applications in therapeutics invention beyond those case studies discussed herein. Accordingly, they may be considered strategic trends worthy of note in advancing the field toward novel ways of addressing pharmacotherapeutically unmet medical needs.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479890","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}
Pub Date : 2024-02-01DOI: 10.1080/17460441.2023.2285402
Hidayat Hussain
{"title":"How can we unlock the full potential of marine biological resources for novel drug discovery in an effective and ethical way?","authors":"Hidayat Hussain","doi":"10.1080/17460441.2023.2285402","DOIUrl":"10.1080/17460441.2023.2285402","url":null,"abstract":"","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138295026","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}