Handbook of experimental pharmacology最新文献

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Life Science Incubation at LabCentral/BioLabs with Partners Extending from the USA to Europe. 在 LabCentral/BioLabs 进行生命科学孵化,合作伙伴从美国扩展到欧洲。
Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_727
Johannes Fruehauf
{"title":"Life Science Incubation at LabCentral/BioLabs with Partners Extending from the USA to Europe.","authors":"Johannes Fruehauf","doi":"10.1007/164_2024_727","DOIUrl":"10.1007/164_2024_727","url":null,"abstract":"<p><p>This chapter provides a blueprint for accelerating biotech and life sciences innovation using public-private partnerships to create innovation infrastructure that become a platform for scientific breakthroughs and economic growth. Examples are provided on creating standalone co-working labs as well as through partnerships with academic and healthcare system partners both in the United States and Europe. Risks and challenges are addressed as well as the overall benefits to the broader public of investing public funds in biotech and life science infrastructure versus individual companies based on the potential impact to global public health from new treatments, therapies, devices, and diagnostics.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"97-112"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Alliance Between the German Cancer Research Center and Bayer: A Retrospective of an Innovative Collaboration Model. 德国癌症研究中心与拜耳的联盟:创新合作模式回顾。
Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_726
A Zuccotti, R Carretero, H Hess-Stumpp
{"title":"The Alliance Between the German Cancer Research Center and Bayer: A Retrospective of an Innovative Collaboration Model.","authors":"A Zuccotti, R Carretero, H Hess-Stumpp","doi":"10.1007/164_2024_726","DOIUrl":"10.1007/164_2024_726","url":null,"abstract":"<p><p>In 2009, the German Cancer Research Center (DKFZ) and the biopharmaceutical company Bayer AG initiated an academic-industry co-discovery collaboration. The partners combined their expertise in tumor biology and drug discovery to identify and validate novel targets for cancer treatment. In the early phase of the Alliance, the focus was on target identification and validation projects. Over time, both partners realized that they could also successfully collaborate on later stages of drug discovery. As a result over the past few years, and following several contract extensions, the two partners have collaborated on several late-stage drug discovery projects. This has resulted in the achievement of several drug discovery milestones and the initiation of early clinical trials, the most recent in 2022. This success has been possible thanks to both partners' understanding of each other's needs and challenges. They jointly developed solutions to issues such as the intrinsic potential conflict of early publishing versus patent protection. Both partners also appreciated the risks involved in some of the experiments, such as starting a joint laboratory for immune-therapy with scientists from both parties working bench-to-bench. Recently, despite these successes the partners decided to terminate the Alliance, as Bayer AG wants to focus its activities on the development of its late pipeline.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"83-95"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Natural Products Drug Discovery: On Silica or In-Silico? 天然产物药物发现:二氧化硅还是硅基?
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2022_611
Hye Kyong Kim, Young Hae Choi, Robert Verpoorte
{"title":"Natural Products Drug Discovery: On Silica or In-Silico?","authors":"Hye Kyong Kim,&nbsp;Young Hae Choi,&nbsp;Robert Verpoorte","doi":"10.1007/164_2022_611","DOIUrl":"https://doi.org/10.1007/164_2022_611","url":null,"abstract":"<p><p>Natural products have been the most important source for drug development throughout the human history. Over time, the formulation of drugs has evolved from crude drugs to refined chemicals. In modern drug discovery, conventional natural products lead-finding usually uses a top-down approach, namely bio-guided fractionation. In this approach, the crude extracts are separated by chromatography and resulting fractions are tested for activity. Subsequently, active fractions are further refined until a single active compound is obtained. However, this is a painstakingly slow and expensive process. Among the alternatives that have been developed to improve this situation, metabolomics has proved to yield interesting results having been applied successfully to drug discovery in the last two decades. The metabolomics-based approach in lead-finding comprises two steps: (1) in-depth chemical profiling of target samples, e.g. plant extracts, and bioactivity assessment, (2) correlation of the chemical and biological data by chemometrics. In the first step of this approach, the target samples are chemically profiled in an untargeted manner to detect as many compounds as possible. So far, NMR spectroscopy, LC-MS, GC-MS, and MS/MS spectrometry are the most common profiling tools. The profile data are correlated with the biological activity with the help of various chemometric methods such as multivariate data analysis. This in-silico analysis has a high potential to replace or complement conventional on-silica bioassay-guided fractionation as it will greatly reduce the number of bioassays, and thus time and costs. Moreover, it may reveal synergistic mechanisms, when present, something for which the classical top-down approach is clearly not suited. This chapter aims to give an overview of successful approaches based on the application of chemical profiling with chemometrics in natural products drug discovery.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":"277 ","pages":"117-141"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9095787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Harnessing Human Pluripotent Stem Cell-Derived Pancreatic In Vitro Models for High-Throughput Toxicity Testing and Diabetes Drug Discovery. 利用人类多能干细胞衍生的胰腺体外模型进行高通量毒性测试和糖尿病药物发现。
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2023_655
Carmen Ching, Elhadi Iich, Adrian Kee Keong Teo
{"title":"Harnessing Human Pluripotent Stem Cell-Derived Pancreatic In Vitro Models for High-Throughput Toxicity Testing and Diabetes Drug Discovery.","authors":"Carmen Ching, Elhadi Iich, Adrian Kee Keong Teo","doi":"10.1007/164_2023_655","DOIUrl":"10.1007/164_2023_655","url":null,"abstract":"<p><p>The long-standing goals in diabetes research are to improve β-cell survival, functionality and increase β-cell mass. Current strategies to manage diabetes progression are still not ideal for sustained maintenance of normoglycemia, thereby increasing demand for the development of novel drugs. Available pancreatic cell lines, cadaveric islets, and their culture methods and formats, either 2D or 3D, allow for multiple avenues of experimental design to address diverse aims in the research setting. More specifically, these pancreatic cells have been employed in toxicity testing, diabetes drug screens, and with careful curation, can be optimized for use in efficient high-throughput screenings (HTS). This has since spearheaded the understanding of disease progression and related mechanisms, as well as the discovery of potential drug candidates which could be the cornerstone for diabetes treatment. This book chapter will touch on the pros and cons of the most widely used pancreatic cells, including the more recent human pluripotent stem cell-derived pancreatic cells, and HTS strategies (cell models, design, readouts) that can be used for the purpose of toxicity testing and diabetes drug discovery.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"301-332"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9613854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biological and Clinical Implications of Sex-Specific Differences in Alzheimer's Disease. 阿尔茨海默病性别特异性差异的生物学和临床意义。
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2023_672
Jose A Santiago, Judith A Potashkin
{"title":"Biological and Clinical Implications of Sex-Specific Differences in Alzheimer's Disease.","authors":"Jose A Santiago,&nbsp;Judith A Potashkin","doi":"10.1007/164_2023_672","DOIUrl":"10.1007/164_2023_672","url":null,"abstract":"<p><p>Mounting evidence indicates that the female sex is a risk factor for Alzheimer's disease (AD), the most common cause of dementia worldwide. Decades of research suggest that sex-specific differences in genetics, environmental factors, hormones, comorbidities, and brain structure and function may contribute to AD development. However, although significant progress has been made in uncovering specific genetic factors and biological pathways, the precise mechanisms underlying sex-biased differences are not fully characterized. Here, we review several lines of evidence, including epidemiological, clinical, and molecular studies addressing sex differences in AD. In addition, we discuss the challenges and future directions in advancing personalized treatments for AD.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"181-197"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9827161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex-Gender-Based Differences in Metabolic Diseases. 代谢性疾病中基于性别的差异。
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2023_683
Ilaria Campesi, Margherita Ruoppolo, Flavia Franconi, Marianna Caterino, Michele Costanzo
{"title":"Sex-Gender-Based Differences in Metabolic Diseases.","authors":"Ilaria Campesi,&nbsp;Margherita Ruoppolo,&nbsp;Flavia Franconi,&nbsp;Marianna Caterino,&nbsp;Michele Costanzo","doi":"10.1007/164_2023_683","DOIUrl":"10.1007/164_2023_683","url":null,"abstract":"<p><p>Sexual dimorphism creates different biological and cellular activities and selective regulation mechanisms in males and females, thus generating differential responses in health and disease. In this scenario, the sex itself is a source of physiologic metabolic disparities that depend on constitutive genetic and epigenetic features that characterize in a specific manner one sex or the other. This has as a direct consequence a huge impact on the metabolic routes that drive the phenotype of an individual. The impact of sex is being clearly recognized also in disease, whereas male and females are more prone to the development of some disorders, or have selective responses to drugs and therapeutic treatments. Actually, very less is known regarding the probable differences guided by sex in the context of inherited metabolic disorders, owing to the scarce consideration of sex in such restricted field, accompanied by an intrinsic bias connected with the rarity of such diseases. Metabolomics technologies have been ultimately developed and adopted for being excellent tools for the investigation of metabolic mechanisms, for marker discovery or monitoring, and for supporting diagnostic procedures of metabolic disorders. Hence, metabolomic approaches can excellently embrace the discovery of sex differences, especially when associated to the outcome or the management of certain inborn errors of the metabolism.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"241-257"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex Differences in Pharmacokinetics. 药物动力学中的性别差异。
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2023_669
Irving Zucker, Brian J Prendergast
{"title":"Sex Differences in Pharmacokinetics.","authors":"Irving Zucker,&nbsp;Brian J Prendergast","doi":"10.1007/164_2023_669","DOIUrl":"10.1007/164_2023_669","url":null,"abstract":"<p><p>Because women have been excluded from most clinical trials, assessment of sex differences in pharmacokinetics is available for a minority of currently prescribed drugs. In a 2020 analysis, substantial pharmacokinetic (PK) sex differences were established for 86 drugs: women given the same drug dose as men routinely generated higher blood concentrations and longer drug elimination times than men. 96% of drugs with higher PK values in women were associated with a higher incidence of adverse drug reactions (ADRs) in women than men; in the small number of instances when PKs of men exceeded those of women, this sex difference positively predicted male-biased ADRs in only 29% of cases. The absence of sex-stratified PK information for many medications raises the concern that sex differences in pharmacokinetics may be widespread and of clinical significance, contributing to sex-specific patterns of ADRs. Administering equal drug doses to women and men neglects sex differences in pharmacokinetics and body weight, risks overmedication of women, and contributes to female-biased ADRs. Evidence-based dosing adjustments are recommended to counteract this sex bias.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"25-39"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9773481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
CaV3.2 (CACNA1H) in Primary Aldosteronism. 原发性醛固酮增多症的CaV3.2 (CACNA1H)。
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2023_660
Hoang An Dinh, Gabriel Stölting, Ute I Scholl
{"title":"Ca<sub>V</sub>3.2 (CACNA1H) in Primary Aldosteronism.","authors":"Hoang An Dinh,&nbsp;Gabriel Stölting,&nbsp;Ute I Scholl","doi":"10.1007/164_2023_660","DOIUrl":"https://doi.org/10.1007/164_2023_660","url":null,"abstract":"<p><p>Aldosterone is a steroid hormone produced in the zona glomerulosa (ZG) of the adrenal cortex. The most prominent function of aldosterone is the control of electrolyte homeostasis and blood pressure via the kidneys. The primary factors regulating aldosterone synthesis are the serum concentrations of angiotensin II and potassium. The T-type voltage-gated calcium channel Ca<sub>V</sub>3.2 (encoded by CACNA1H) is an important component of electrical as well as intracellular calcium oscillations, which govern aldosterone production in the ZG. Excessive aldosterone production that is (partially) uncoupled from physiological stimuli leads to primary aldosteronism, the most common cause of secondary hypertension. Germline gain-of-function mutations in CACNA1H were identified in familial hyperaldosteronism, whereas somatic mutations are a rare cause of aldosterone-producing adenomas. In this review, we summarize these findings, put them in perspective, and highlight missing knowledge.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":"279 ","pages":"249-262"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9919953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiac Disease Modeling with Engineered Heart Tissue. 用工程化心脏组织建模心脏病。
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2023_681
Lin Cai, Ruxiang Wang, Donghui Zhang
{"title":"Cardiac Disease Modeling with Engineered Heart Tissue.","authors":"Lin Cai, Ruxiang Wang, Donghui Zhang","doi":"10.1007/164_2023_681","DOIUrl":"10.1007/164_2023_681","url":null,"abstract":"<p><p>The rhythmically beating heart is the foundation of life-sustaining blood flow. There are four chambers and many different types of cell in the heart, but the twisted myofibrillar structures formed by cardiomyocytes are particularly important for cardiac contraction and electrical impulse transmission properties. The ability to generate cardiomyocytes using human-induced pluripotent stem cells has essentially solved the cell supply shortage for in vitro simulation of cardiac tissue function; however, modeling heart at the tissue level needs mature myocardial structure, electrophysiology, and contractile characteristics. Here, the current research on human functionalized cardiac microtissue in modeling cardiac diseases is reviewed and the design criteria and practical applications of different human engineered heart tissues, including cardiac organoids, cardiac thin films, and cardiac microbundles are analyzed. Table summarizing the ability of several in vitro myocardial models to assess heart structure and function for cardiac disease modeling.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"235-255"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9977248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Precision Medicine in Therapy of Non-solid Cancer. 精准医学在非实体肿瘤治疗中的应用。
Handbook of experimental pharmacology Pub Date : 2023-01-01 DOI: 10.1007/164_2022_608
Ines Schmidts, Torsten Haferlach, Gregor Hoermann
{"title":"Precision Medicine in Therapy of Non-solid Cancer.","authors":"Ines Schmidts,&nbsp;Torsten Haferlach,&nbsp;Gregor Hoermann","doi":"10.1007/164_2022_608","DOIUrl":"https://doi.org/10.1007/164_2022_608","url":null,"abstract":"<p><p>The development and approval of the tyrosine kinase inhibitor imatinib in 2001 has heralded the advance of directed therapy options. Today, an armamentarium of targeted therapeutics is available and enables the use of precision medicine in non-solid cancer. Precision medicine is guided by the detection of tumor-specific and targetable characteristics. These include pathogenic fusions and/or mutations, dependency on specific signaling pathways, and the expression of certain cell surface markers. Within the first part, we review approved targeted therapies for the compound classes of small molecule inhibitors, antibody-based therapies and cellular therapies. Particular consideration is given to the underlying pathobiology and the respective mechanism of action. The second part emphasizes on how biomarkers, whether they are of diagnostic, prognostic, or predictive relevance, are indispensable tools to guide therapy choice and management in precision medicine. Finally, the examples of acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia illustrate how integration of these biomarkers helps to tailor therapy.</p>","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":"280 ","pages":"35-64"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10141945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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