Pub Date : 2024-08-22DOI: 10.1016/j.drudis.2024.104144
Chemical probes and chemogenomic compounds are valuable tools to link gene to phenotype, explore human biology, and uncover novel targets for precision medicine. The mission of the Target 2035 initiative is to discover chemical tools for all human proteins by the year 2035. Here, we draw a landscape of the current chemical coverage of human biological pathways. Although available chemical tools target only 3% of the human proteome, they already cover 53% of human biological pathways and represent a versatile toolkit to dissect a vast portion of human biology. Pathways targeted by existing drugs may be enriched in unknown but valid drug targets and could be prioritized in future Target 2035 efforts.
{"title":"Chemical coverage of human biological pathways","authors":"","doi":"10.1016/j.drudis.2024.104144","DOIUrl":"10.1016/j.drudis.2024.104144","url":null,"abstract":"<div><p>Chemical probes and chemogenomic compounds are valuable tools to link gene to phenotype, explore human biology, and uncover novel targets for precision medicine. The mission of the Target 2035 initiative is to discover chemical tools for all human proteins by the year 2035. Here, we draw a landscape of the current chemical coverage of human biological pathways. Although available chemical tools target only 3% of the human proteome, they already cover 53% of human biological pathways and represent a versatile toolkit to dissect a vast portion of human biology. Pathways targeted by existing drugs may be enriched in unknown but valid drug targets and could be prioritized in future Target 2035 efforts.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624002691/pdfft?md5=fd391cdfa8c932ff2a0d499beadcdad0&pid=1-s2.0-S1359644624002691-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142045994","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 : 2024-08-22DOI: 10.1016/j.drudis.2024.104143
Identification of high-quality hit chemical matter is of vital importance to the success of drug discovery campaigns. However, this goal is becoming ever harder to achieve as the targets entering the portfolios of pharmaceutical and biotechnology companies are increasingly trending towards novel and traditionally challenging to drug. This demand has fuelled the development and adoption of numerous new screening approaches, whereby the contemporary hit identification toolbox comprises a growing number of orthogonal and complementary technologies including high-throughput screening, fragment-based ligand design, affinity screening (affinity-selection mass spectrometry, differential scanning fluorimetry, DNA-encoded library screening), as well as increasingly sophisticated computational predictive approaches. Herein we describe how an integrated strategy for hit discovery, whereby multiple hit identification techniques are tactically applied, selected in the context of target suitability and resource priority, represents an optimal and often essential approach to maximise the likelihood of identifying quality starting points from which to develop the next generation of medicines.
{"title":"Hit me with your best shot: Integrated hit discovery for the next generation of drug targets","authors":"","doi":"10.1016/j.drudis.2024.104143","DOIUrl":"10.1016/j.drudis.2024.104143","url":null,"abstract":"<div><p>Identification of high-quality hit chemical matter is of vital importance to the success of drug discovery campaigns. However, this goal is becoming ever harder to achieve as the targets entering the portfolios of pharmaceutical and biotechnology companies are increasingly trending towards novel and traditionally challenging to drug. This demand has fuelled the development and adoption of numerous new screening approaches, whereby the contemporary hit identification toolbox comprises a growing number of orthogonal and complementary technologies including high-throughput screening, fragment-based ligand design, affinity screening (affinity-selection mass spectrometry, differential scanning fluorimetry, DNA-encoded library screening), as well as increasingly sophisticated computational predictive approaches. Herein we describe how an integrated strategy for hit discovery, whereby multiple hit identification techniques are tactically applied, selected in the context of target suitability and resource priority, represents an optimal and often essential approach to maximise the likelihood of identifying quality starting points from which to develop the next generation of medicines.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034737","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 : 2024-08-19DOI: 10.1016/j.drudis.2024.104142
Currently, various antimitotic inhibitors applied in tumor therapy. However, these inhibitors exhibit targeted toxicity to some extent. As a motor protein, kinesin family member 18A (KIF18A) is crucial to spindle formation and is associated with tumors exhibiting ploidy-specific characteristics such as chromosomal aneuploidy, whole-genome doubling (WGD), and chromosomal instability (CIN). Differing from traditional antimitotic targets, KIF18A exhibits tumor-specific selectivity. The functional loss or attenuation of KIF18A results in vulnerability of tumor cells with ploidy-specific characteristics, with lesser effects on diploid cells. Research on inhibitors targeting KIF18A with ploidy-specific lethality holds significant importance. This review provides a brief overview of the regulatory mechanisms of the ploidy-specific lethality target KIF18A and the research advancements in its inhibitors, aiming to facilitate the development of KIF18A inhibitors.
{"title":"Exploration of inhibitors targeting KIF18A with ploidy-specific lethality","authors":"","doi":"10.1016/j.drudis.2024.104142","DOIUrl":"10.1016/j.drudis.2024.104142","url":null,"abstract":"<div><p>Currently, various antimitotic inhibitors applied in tumor therapy. However, these inhibitors exhibit targeted toxicity to some extent. As a motor protein, kinesin family member 18A (KIF18A) is crucial to spindle formation and is associated with tumors exhibiting ploidy-specific characteristics such as chromosomal aneuploidy, whole-genome doubling (WGD), and chromosomal instability (CIN). Differing from traditional antimitotic targets, KIF18A exhibits tumor-specific selectivity. The functional loss or attenuation of KIF18A results in vulnerability of tumor cells with ploidy-specific characteristics, with lesser effects on diploid cells. Research on inhibitors targeting KIF18A with ploidy-specific lethality holds significant importance. This review provides a brief overview of the regulatory mechanisms of the ploidy-specific lethality target KIF18A and the research advancements in its inhibitors, aiming to facilitate the development of KIF18A inhibitors.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015828","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 : 2024-08-19DOI: 10.1016/j.drudis.2024.104141
Orthosteric and allosteric modulators, which constitute the majority of current drugs, bind to the orthosteric and allosteric sites of target proteins, respectively. However, the clinical efficacy of these agents is frequently compromised by poor selectivity or reduced potency. Dualsteric modulators feature two linked pharmacophores that bind to orthosteric and allosteric sites of the target proteins simultaneously, thereby offering a promising avenue to achieve both potency and specificity. In this review, we summarize recent structures available for dualsteric modulators in complex with their target proteins, elucidating detailed drug–target interactions and dualsteric action patterns. Moreover, we provide a design and optimization strategy for dualsteric modulators based on structure-based drug design approaches.
{"title":"Designed dualsteric modulators: A novel route for drug discovery","authors":"","doi":"10.1016/j.drudis.2024.104141","DOIUrl":"10.1016/j.drudis.2024.104141","url":null,"abstract":"<div><p>Orthosteric and allosteric modulators, which constitute the majority of current drugs, bind to the orthosteric and allosteric sites of target proteins, respectively. However, the clinical efficacy of these agents is frequently compromised by poor selectivity or reduced potency. Dualsteric modulators feature two linked pharmacophores that bind to orthosteric and allosteric sites of the target proteins simultaneously, thereby offering a promising avenue to achieve both potency and specificity. In this review, we summarize recent structures available for dualsteric modulators in complex with their target proteins, elucidating detailed drug–target interactions and dualsteric action patterns. Moreover, we provide a design and optimization strategy for dualsteric modulators based on structure-based drug design approaches.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015827","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 : 2024-08-19DOI: 10.1016/j.drudis.2024.104140
Glioblastoma multiforme (GBM) is a highly severe primary brain tumor. Despite extensive research, effective treatments remain elusive. Long noncoding RNAs (lncRNAs) play a significant role in both cancer and normal biology. They influence alternative splicing (AS), which is crucial in cancer. Advances in lncRNA-specific microarrays and next-generation sequencing have enhanced understanding of AS. Abnormal AS contributes to cancer invasion, metastasis, apoptosis, therapeutic resistance, and tumor development, including glioma. lncRNA-mediated AS affects several cellular signaling pathways, promoting or suppressing cancer malignancy. This review discusses the lncRNAs regulating AS in glioblastoma and their mechanisms.
{"title":"Role of long noncoding RNAs in the regulation of alternative splicing in glioblastoma","authors":"","doi":"10.1016/j.drudis.2024.104140","DOIUrl":"10.1016/j.drudis.2024.104140","url":null,"abstract":"<div><p>Glioblastoma multiforme (GBM) is a highly severe primary brain tumor. Despite extensive research, effective treatments remain elusive. Long noncoding RNAs (lncRNAs) play a significant role in both cancer and normal biology. They influence alternative splicing (AS), which is crucial in cancer. Advances in lncRNA-specific microarrays and next-generation sequencing have enhanced understanding of AS. Abnormal AS contributes to cancer invasion, metastasis, apoptosis, therapeutic resistance, and tumor development, including glioma. lncRNA-mediated AS affects several cellular signaling pathways, promoting or suppressing cancer malignancy. This review discusses the lncRNAs regulating AS in glioblastoma and their mechanisms.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015829","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 : 2024-08-19DOI: 10.1016/j.drudis.2024.104138
Patients diagnosed with rare diseases and their and families search desperately to organize drug discovery campaigns. Alternative models that differ from default paradigms offer real opportunities. There are, however, no clear guidelines for the development of such models, which reduces success rates and raises costs. We address the main challenges in making the discovery of new preclinical treatments more accessible, using rare hereditary paraplegia as a paradigmatic case. First, we discuss the necessary expertise, and the patients’ clinical and genetic data. Then, we revisit gene therapy, de novo drug development, and drug repurposing, discussing their applicability. Moreover, we explore a pool of recommended in silico tools for pathogenic variant and protein structure prediction, virtual screening, and experimental validation methods, discussing their strengths and weaknesses. Finally, we focus on successful case applications.
{"title":"Preclinical alternative drug discovery programs for monogenic rare diseases. Should small molecules or gene therapy be used? The case of hereditary spastic paraplegias","authors":"","doi":"10.1016/j.drudis.2024.104138","DOIUrl":"10.1016/j.drudis.2024.104138","url":null,"abstract":"<div><p>Patients diagnosed with rare diseases and their and families search desperately to organize drug discovery campaigns. Alternative models that differ from default paradigms offer real opportunities. There are, however, no clear guidelines for the development of such models, which reduces success rates and raises costs. We address the main challenges in making the discovery of new preclinical treatments more accessible, using rare hereditary paraplegia as a paradigmatic case. First, we discuss the necessary expertise, and the patients’ clinical and genetic data. Then, we revisit gene therapy, <em>de novo</em> drug development, and drug repurposing, discussing their applicability. Moreover, we explore a pool of recommended <em>in silico</em> tools for pathogenic variant and protein structure prediction, virtual screening, and experimental validation methods, discussing their strengths and weaknesses. Finally, we focus on successful case applications.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624002630/pdfft?md5=e0a5c408341f6d771720acc04c266561&pid=1-s2.0-S1359644624002630-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999059","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 : 2024-08-19DOI: 10.1016/j.drudis.2024.104139
Automatic eligibility criteria parsing in clinical trials is crucial for cohort recruitment leading to data validity and trial completion. Recent years have witnessed an explosion of powerful machine learning (ML) and natural language processing (NLP) models that can streamline the patient accrual process. In this PRISMA-based scoping review, we comprehensively evaluate existing literature on the application of ML/NLP models for parsing clinical trial eligibility criteria. The review covers 9160 papers published between 2000 and 2024, with 88 publications subjected to data charting along 17 dimensions. Our review indicates insufficient use of state-of-the-art artificial intelligence (AI) models in the analysis of clinical protocols.
{"title":"Machine learning and natural language processing in clinical trial eligibility criteria parsing: a scoping review","authors":"","doi":"10.1016/j.drudis.2024.104139","DOIUrl":"10.1016/j.drudis.2024.104139","url":null,"abstract":"<div><p>Automatic eligibility criteria parsing in clinical trials is crucial for cohort recruitment leading to data validity and trial completion. Recent years have witnessed an explosion of powerful machine learning (ML) and natural language processing (NLP) models that can streamline the patient accrual process. In this PRISMA-based scoping review, we comprehensively evaluate existing literature on the application of ML/NLP models for parsing clinical trial eligibility criteria. The review covers 9160 papers published between 2000 and 2024, with 88 publications subjected to data charting along 17 dimensions. Our review indicates insufficient use of state-of-the-art artificial intelligence (AI) models in the analysis of clinical protocols.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999058","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 : 2024-08-14DOI: 10.1016/j.drudis.2024.104137
Hundreds of virtual screening (VS) studies have targeted the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (M-pro) to identify small molecules that inhibit its proteolytic action. Most studies use AutoDock Vina or Glide methodologies [high-throughput VS (HTVS), standard precision (SP), or extra precision (XP)], independently or in a VS workflow. Moreover, the Protein Data Bank (PDB) includes multiple complexes between M-pro and various noncovalent ligands, providing an excellent benchmark for assessing the predictive capabilities of docking programs. Here, we analyze the ability of the three Glide methodologies and AutoDock Vina by using various target structures/preparations to predict the experimental poses of these complexes. Our aims are to optimize target setup and docking methodologies, minimize false positives, and maximize the identification of various chemotypes in a SARS-CoV-2 M-pro noncovalent inhibitor VS campaign.
数以百计的虚拟筛选(VS)研究都以严重急性呼吸系统综合征-冠状病毒 2(SARS-CoV-2)的主要蛋白酶(M-pro)为目标,以鉴定抑制其蛋白水解作用的小分子化合物。大多数研究使用 AutoDock Vina 或 Glide 方法[高通量 VS (HTVS)、标准精度 (SP) 或额外精度 (XP)],独立或在 VS 工作流程中使用。此外,蛋白质数据库(PDB)包含了 M-pro 与各种非共价配体之间的多个复合物,为评估对接程序的预测能力提供了一个极好的基准。在这里,我们通过使用各种目标结构/制剂来预测这些复合物的实验姿势,分析了三种 Glide 方法和 AutoDock Vina 的能力。我们的目的是优化目标设置和对接方法,尽量减少假阳性,并在 SARS-CoV-2 M-pro 非共价抑制剂 VS 活动中最大限度地识别各种化学类型。
{"title":"Are protein–ligand docking programs good enough to predict experimental poses of noncovalent ligands bound to the SARS-CoV-2 main protease?","authors":"","doi":"10.1016/j.drudis.2024.104137","DOIUrl":"10.1016/j.drudis.2024.104137","url":null,"abstract":"<div><p>Hundreds of virtual screening (VS) studies have targeted the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (M-pro) to identify small molecules that inhibit its proteolytic action. Most studies use AutoDock Vina or Glide methodologies [high-throughput VS (HTVS), standard precision (SP), or extra precision (XP)], independently or in a VS workflow. Moreover, the Protein Data Bank (PDB) includes multiple complexes between M-pro and various noncovalent ligands, providing an excellent benchmark for assessing the predictive capabilities of docking programs. Here, we analyze the ability of the three Glide methodologies and AutoDock Vina by using various target structures/preparations to predict the experimental poses of these complexes. Our aims are to optimize target setup and docking methodologies, minimize false positives, and maximize the identification of various chemotypes in a SARS-CoV-2 M-pro noncovalent inhibitor VS campaign.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994909","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 : 2024-08-06DOI: 10.1016/j.drudis.2024.104136
This study conducted policy and regulation analyses and user acceptance surveys in three East Asian countries with developed telecommunication infrastructure (China, South Korea, and Japan) to determine the most effective way to implement mobile health (mHealth). Regional differences in users’ emphasis on the purpose of mHealth, including medical information referral or health management, appear to be influenced by regional regulation, thus making regulation analysis important when considering mHealth penetration strategies. Potential mHealth users have high expectations for medical information and correspondence, which is crucial for the pharmaceutical industry in terms of providing information and retaining patients. Furthermore, potential users are willing to use the system medically, which is beneficial to the pharmaceutical industry when introducing mHealth and prescriptions in combination.
{"title":"Promoting the social implementation of digital and mobile health: effects of regulation on user and non-user behavior in East Asia","authors":"","doi":"10.1016/j.drudis.2024.104136","DOIUrl":"10.1016/j.drudis.2024.104136","url":null,"abstract":"<div><p>This study conducted policy and regulation analyses and user acceptance surveys in three East Asian countries with developed telecommunication infrastructure (China, South Korea, and Japan) to determine the most effective way to implement mobile health (mHealth). Regional differences in users’ emphasis on the purpose of mHealth, including medical information referral or health management, appear to be influenced by regional regulation, thus making regulation analysis important when considering mHealth penetration strategies. Potential mHealth users have high expectations for medical information and correspondence, which is crucial for the pharmaceutical industry in terms of providing information and retaining patients. Furthermore, potential users are willing to use the system medically, which is beneficial to the pharmaceutical industry when introducing mHealth and prescriptions in combination.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624002617/pdfft?md5=9f4bb18440e57af47ac64b4282921428&pid=1-s2.0-S1359644624002617-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905296","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 : 2024-08-05DOI: 10.1016/j.drudis.2024.104128
This article addresses the research and development (R&D) productivity challenge of the pharmaceutical industry, focusing on United States Food and Drug Administration (FDA)-related new drug approvals of the top 20 pharmaceutical companies (2014–2023). We evaluated the degree of innovation in new drugs to determine the innovativeness of these leading companies. A key finding of our analysis is the decline in the number of new drugs approved by the FDA for these leading companies over the investigated time period. This trend suggests that some of the leading companies are losing ground in R&D innovation, raising concerns about their ability to sustain competitive advantage, ensure long-term market success, and maintain viable business models.
{"title":"Comparative analysis of FDA approvals by top 20 pharma companies (2014–2023)","authors":"","doi":"10.1016/j.drudis.2024.104128","DOIUrl":"10.1016/j.drudis.2024.104128","url":null,"abstract":"<div><p>This article addresses the research and development (R&D) productivity challenge of the pharmaceutical industry, focusing on United States Food and Drug Administration (FDA)-related new drug approvals of the top 20 pharmaceutical companies (2014–2023). We evaluated the degree of innovation in new drugs to determine the innovativeness of these leading companies. A key finding of our analysis is the decline in the number of new drugs approved by the FDA for these leading companies over the investigated time period. This trend suggests that some of the leading companies are losing ground in R&D innovation, raising concerns about their ability to sustain competitive advantage, ensure long-term market success, and maintain viable business models.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624002538/pdfft?md5=41432e6fdcef9771d76b188b79fa8261&pid=1-s2.0-S1359644624002538-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887850","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}