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  Subjects -> MEDICAL SCIENCES (Total: 7245 journals)
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MEDICAL SCIENCES (1802 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 3562 Journals sorted alphabetically
16 de Abril     Open Access  
AADE in Practice     Hybrid Journal   (Followers: 4)
ABCS Health Sciences     Open Access   (Followers: 1)
Abia State University Medical Students' Association Journal     Full-text available via subscription  
ACIMED     Open Access   (Followers: 1)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
Acta Bio Medica     Full-text available via subscription   (Followers: 2)
Acta Bioethica     Open Access   (Followers: 1)
Acta Bioquimica Clinica Latinoamericana     Open Access   (Followers: 1)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Informatica Medica     Open Access   (Followers: 1)
Acta Medica Bulgarica     Open Access  
Acta Medica Colombiana     Open Access   (Followers: 1)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Medica Indonesiana     Open Access  
Acta medica Lituanica     Open Access  
Acta Medica Marisiensis     Open Access  
Acta Medica Martiniana     Open Access  
Acta Medica Nagasakiensia     Open Access  
Acta Medica Peruana     Open Access   (Followers: 2)
Acta Médica Portuguesa     Open Access  
Acta Medica Saliniana     Open Access  
Acta Scientiarum. Health Sciences     Open Access  
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 2)
Addiction Science & Clinical Practice     Open Access   (Followers: 7)
Addictive Behaviors Reports     Open Access   (Followers: 6)
Advanced Health Care Technologies     Open Access   (Followers: 4)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 7)
Advances in Bioscience and Clinical Medicine     Open Access   (Followers: 5)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29)
Advances in Life Course Research     Hybrid Journal   (Followers: 8)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Medical Education and Practice     Open Access   (Followers: 26)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Medicine     Open Access   (Followers: 2)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4)
Advances in Molecular Oncology     Open Access   (Followers: 1)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 8)
Advances in Parkinson's Disease     Open Access  
Advances in Phytomedicine     Full-text available via subscription  
Advances in Preventive Medicine     Open Access   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Therapy     Hybrid Journal   (Followers: 5)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5)
Advances in Wound Care     Hybrid Journal   (Followers: 10)
African Health Sciences     Open Access   (Followers: 2)
African Journal of Biomedical Research     Open Access  
African Journal of Clinical and Experimental Microbiology     Open Access   (Followers: 1)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
African Journal of Medical and Health Sciences     Open Access   (Followers: 2)
African Journal of Trauma     Open Access  
Afrimedic Journal     Open Access   (Followers: 2)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 8)
AJOB Primary Research     Partially Free   (Followers: 3)
Aktuelle Ernährungsmedizin     Hybrid Journal   (Followers: 4)
Al-Azhar Assiut Medical Journal     Open Access  
Alexandria Journal of Medicine     Open Access   (Followers: 1)
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 2)
Alpha Omegan     Full-text available via subscription  
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
American Journal of Biomedical Engineering     Open Access   (Followers: 11)
American Journal of Biomedical Research     Open Access   (Followers: 2)
American Journal of Biomedicine     Full-text available via subscription   (Followers: 6)
American Journal of Chinese Medicine, The     Hybrid Journal   (Followers: 5)
American Journal of Clinical Medicine Research     Open Access   (Followers: 5)
American Journal of Family Therapy     Hybrid Journal   (Followers: 11)
American Journal of Law & Medicine     Full-text available via subscription   (Followers: 12)
American Journal of Lifestyle Medicine     Hybrid Journal   (Followers: 5)
American Journal of Managed Care     Full-text available via subscription   (Followers: 11)
American Journal of Medical Case Reports     Open Access   (Followers: 1)
American Journal of Medical Sciences and Medicine     Open Access   (Followers: 1)
American Journal of Medicine     Hybrid Journal   (Followers: 46)
American Journal of Medicine and Medical Sciences     Open Access   (Followers: 1)
American Journal of Medicine Studies     Open Access  
American Journal of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American Journal of the Medical Sciences     Hybrid Journal   (Followers: 12)
American Journal on Addictions     Hybrid Journal   (Followers: 9)
American Medical Journal     Open Access   (Followers: 4)
American medical news     Free   (Followers: 3)
American Medical Writers Association Journal     Full-text available via subscription   (Followers: 2)
Amyloid: The Journal of Protein Folding Disorders     Hybrid Journal   (Followers: 4)
Anales de la Facultad de Medicina     Open Access  
Anales de la Facultad de Medicina, Universidad de la República, Uruguay     Open Access  
Anales del Sistema Sanitario de Navarra     Open Access   (Followers: 1)
Analgesia & Resuscitation : Current Research     Hybrid Journal   (Followers: 3)
Anatomical Science International     Hybrid Journal   (Followers: 2)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1)
Anatomy Research International     Open Access   (Followers: 2)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3)
Annales de Pathologie     Full-text available via subscription  
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annals of African Medicine     Open Access   (Followers: 1)
Annals of Anatomy - Anatomischer Anzeiger     Hybrid Journal   (Followers: 2)
Annals of Bioanthropology     Open Access   (Followers: 3)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18)
Annals of Biomedical Sciences     Full-text available via subscription   (Followers: 3)
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 8)
Annals of Family Medicine     Open Access   (Followers: 13)
Annals of Fundeni Hospital     Open Access   (Followers: 1)
Annals of Ibadan Postgraduate Medicine     Open Access  
Annals of Medical and Health Sciences Research     Open Access   (Followers: 7)
Annals of Medicine     Hybrid Journal   (Followers: 12)
Annals of Medicine and Surgery     Open Access   (Followers: 5)
Annals of Microbiology     Hybrid Journal   (Followers: 10)
Annals of Nigerian Medicine     Open Access   (Followers: 1)
Annals of Saudi Medicine     Open Access  
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5)
Annals of The Royal College of Surgeons of England     Full-text available via subscription   (Followers: 3)
Annual Reports in Medicinal Chemistry     Full-text available via subscription   (Followers: 7)
Annual Reports on NMR Spectroscopy     Full-text available via subscription   (Followers: 4)
Annual Review of Medicine     Full-text available via subscription   (Followers: 18)
Anthropological Review     Open Access   (Followers: 24)
Anthropologie et santé     Open Access   (Followers: 5)
Antibiotics     Open Access   (Followers: 9)
Antibodies     Open Access   (Followers: 2)
Antibody Technology Journal     Open Access   (Followers: 1)
Anuradhapura Medical Journal     Open Access  
Anwer Khan Modern Medical College Journal     Open Access   (Followers: 2)
Apmis     Hybrid Journal   (Followers: 1)
Apparence(s)     Open Access   (Followers: 1)
Applied Clinical Informatics     Hybrid Journal   (Followers: 2)
Applied Medical Informatics     Open Access   (Followers: 11)
Arab Journal of Nephrology and Transplantation     Open Access   (Followers: 1)
Arak Medical University Journal     Open Access  
Archive of Clinical Medicine     Open Access   (Followers: 1)
Archive of Community Health     Open Access  
Archives of Biomedical Sciences     Open Access   (Followers: 7)
Archives of Medical and Biomedical Research     Open Access   (Followers: 3)
Archives of Medical Laboratory Sciences     Open Access   (Followers: 1)
Archives of Medicine and Health Sciences     Open Access   (Followers: 3)
Archives of Trauma Research     Open Access   (Followers: 2)
Archivos de Medicina (Manizales)     Open Access  
ArgoSpine News & Journal     Hybrid Journal  
Arquivos Brasileiros de Oftalmologia     Open Access  
Arquivos de Ciências da Saúde     Open Access  
Arquivos de Medicina     Open Access  
ARS Medica Tomitana     Open Access   (Followers: 1)
Art Therapy: Journal of the American Art Therapy Association     Full-text available via subscription   (Followers: 10)
Arterial Hypertension     Open Access  
Artificial Intelligence in Medicine     Hybrid Journal   (Followers: 12)
Artificial Organs     Hybrid Journal   (Followers: 1)
Asia Pacific Family Medicine     Open Access  
Asia Pacific Journal of Clinical Nutrition     Full-text available via subscription   (Followers: 9)
Asia Pacific Journal of Clinical Trials : Nervous System Diseases     Open Access  
Asian Bioethics Review     Full-text available via subscription   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 6)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 2)
Asian Journal of Medical and Pharmaceutical Researches     Open Access   (Followers: 1)
Asian Journal of Medical Sciences     Open Access   (Followers: 1)
Asian Journal of Scientific Research     Open Access   (Followers: 2)
Asian Journal of Transfusion Science     Open Access   (Followers: 2)
Asian Medicine     Hybrid Journal   (Followers: 4)
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
Atención Familiar     Open Access  
Atención Primaria     Open Access   (Followers: 1)
Audiology - Communication Research     Open Access   (Followers: 8)
Auris Nasus Larynx     Full-text available via subscription  
Australian Coeliac     Full-text available via subscription   (Followers: 2)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 1)
Autopsy and Case Reports     Open Access  
Aviation, Space, and Environmental Medicine     Full-text available via subscription   (Followers: 10)
Avicenna     Open Access   (Followers: 2)
Avicenna Journal of Medicine     Open Access   (Followers: 1)
Bangabandhu Sheikh Mujib Medical University Journal     Open Access   (Followers: 1)
Bangladesh Journal of Anatomy     Open Access   (Followers: 1)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 3)
Bangladesh Journal of Medical Education     Open Access   (Followers: 2)
Bangladesh Journal of Medical Microbiology     Open Access   (Followers: 3)
Bangladesh Journal of Medical Physics     Open Access  
Bangladesh Journal of Medical Science     Open Access  
Bangladesh Journal of Medicine     Open Access   (Followers: 1)
Bangladesh Journal of Physiology and Pharmacology     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 2)
Bangladesh Medical Journal     Open Access  
Bangladesh Medical Journal Khulna     Open Access  
Bangladesh Medical Research Council Bulletin     Open Access  
Basal Ganglia     Hybrid Journal  
Basic Sciences of Medicine     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BC Medical Journal     Free  
Benha Medical Journal     Open Access  
Bijblijven     Hybrid Journal  
Bijzijn     Hybrid Journal   (Followers: 2)
Bijzijn XL     Hybrid Journal   (Followers: 1)
Bio-Algorithms and Med-Systems     Hybrid Journal   (Followers: 1)
Bioelectromagnetics     Hybrid Journal   (Followers: 1)
Bioengineering & Translational Medicine     Open Access  
Bioethics     Hybrid Journal   (Followers: 14)
Bioethics Research Notes     Full-text available via subscription   (Followers: 14)
Biologics in Therapy     Open Access  
Biology of Sex Differences     Open Access   (Followers: 3)
Biomarker Research     Open Access   (Followers: 2)

        1 2 3 4 5 6 7 8 | Last

Journal Cover Annual Reports in Medicinal Chemistry
  [SJR: 0.514]   [H-I: 33]   [7 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 0065-7743
   Published by Elsevier Homepage  [3048 journals]
  • Chapter Ten Chemical Biology in Drug Discovery
    • Authors: M. Paola Castaldi; Andrea Zuhl; Piero Ricchiuto; J. Adam Hendricks
      Pages: 335 - 370
      Abstract: Publication date: 2017
      Source:Annual Reports in Medicinal Chemistry, Volume 50
      Author(s): M. Paola Castaldi, Andrea Zuhl, Piero Ricchiuto, J. Adam Hendricks
      Chemical biology is the broad discipline at the interface of chemistry and biology that has contributed many important advancements to our ability to perturb and probe biological functions. In this chapter, we focus on describing chemical biology methods for target identification, target engagement, and target validation with demonstrative examples from the last few years.

      PubDate: 2017-11-21T07:32:13Z
      DOI: 10.1016/bs.armc.2017.08.009
      Issue No: Vol. 50 (2017)
       
  • Series Page
    • Abstract: Publication date: 2017
      Source:Annual Reports in Medicinal Chemistry, Volume 50


      PubDate: 2017-11-21T07:32:13Z
       
  • Keyword Index, Volume 50
    • Abstract: Publication date: 2017
      Source:Annual Reports in Medicinal Chemistry, Volume 50


      PubDate: 2017-11-21T07:32:13Z
       
  • Cumulative Chapter Titles Keyword Index, Volume 1 – 50
    • Abstract: Publication date: 2017
      Source:Annual Reports in Medicinal Chemistry, Volume 50


      PubDate: 2017-11-21T07:32:13Z
       
  • Cumulative NCE Introduction Index, 1983–2017
    • Abstract: Publication date: 2017
      Source:Annual Reports in Medicinal Chemistry, Volume 50


      PubDate: 2017-11-21T07:32:13Z
       
  • Cumulative NCE Introduction Index, 1983–2017 (by Indication)
    • Abstract: Publication date: 2017
      Source:Annual Reports in Medicinal Chemistry, Volume 50


      PubDate: 2017-11-21T07:32:13Z
       
  • From Natural Peptides to Market
    • Authors: Claudio D. Schteingart; Jolene L. Lau
      Abstract: Publication date: Available online 10 November 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Claudio D. Schteingart, Jolene L. Lau
      Taking as examples the peptides approved in the United States, Europe, and Japan up to June 2017, this chapter examines the transformation of natural peptides into safe and efficacious drugs. Although peptides have higher progression rates from drug candidate selection to Phase 2 than small molecules, a few safety issues specific to peptides need to be considered. Because of their hydrophilicity and molecular weight, peptides can only address molecular targets on the surface of cells or in the extracellular fluid. Peptidic agonists generally are based on the structure of the natural peptide, which provide leads with high potency, but typically insufficient selectivity and poor pharmacokinetic properties, which are improved during drug discovery programs. The switch from agonists to antagonists is achieved by judicious changes of structure, exemplified with several peptides on the market. Multiple examples illustrate how the clearance and half-life of a candidate peptide is tailored to the desired dosing interval, which must be appropriate to the severity of the condition treated. This and the physicochemical properties of the peptide dictate in turn the modes and routes of administration of the drug. Scenarios are suggested where the discovery of a peptide-based drug might be preferable to that of a small molecule.

      PubDate: 2017-11-11T11:48:43Z
      DOI: 10.1016/bs.armc.2017.08.003
       
  • Recent Advances of Microfluidics Technologies in the Field of Medicinal
           Chemistry
    • Authors: László Ürge; Jesus Alcazar; Lena Huck; György Dormán
      Abstract: Publication date: Available online 9 November 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): László Ürge, Jesus Alcazar, Lena Huck, György Dormán
      Microfluidics, mesofluidics, and lab-on-a-chip technologies have been extensively researched in the pharma and life science industry over the last two decades, including synthesis of novel compounds and building blocks, medicinal chemistry support, biological screening, DMPK studies, and formulation and manufacturing of APIs and final products. These technologies can provide significant advantages over traditional methods and have the potential to revolutionize certain aspects of pharma R&D. The recent developments on the application of these novel techniques, their penetration in the industry, and their barriers for the further adaptation will be extensively discussed in this overview.

      PubDate: 2017-11-11T11:48:43Z
      DOI: 10.1016/bs.armc.2017.09.001
       
  • Antibody-Recruiting Small Molecules: Synthetic Constructs as
           Immunotherapeutics
    • Authors: Patrick J. McEnaney; Christopher G. Parker; Andrew X. Zhang
      Abstract: Publication date: Available online 9 November 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Patrick J. McEnaney, Christopher G. Parker, Andrew X. Zhang
      The ability to harness one's endogenous immune response against a pathogen has significantly advanced the treatment of many serious diseases. While immune-based therapeutic strategies have traditionally been dominated by biologics, recent advances at the interface of organic chemistry and immunology have yielded new classes of small molecules that can direct and regulate immune responses. This chapter focuses on the development and application of one such class of small molecules called antibody-recruiting small molecules (ARMs) for the treatment of cancer and infectious diseases. ARMs are bifunctional small molecules that simultaneously bind to a pathogen-associated cell surface biomarker and endogenous antibodies, forming a ternary complex. Formation of the ternary complex then directs antibody dependent, immune effector functions, resulting in targeted cytotoxicity. Here, we present an overview of the conception and evolution of ARMs, including key case studies highlighting their in vitro and in vivo efficacies, as well as some key challenges and perspectives of this area of research in the context of drug discovery and clinical application.

      PubDate: 2017-11-11T11:48:43Z
      DOI: 10.1016/bs.armc.2017.08.008
       
  • A Decade of Deuteration in Medicinal Chemistry
    • Authors: Julie F. Liu; Scott L. Harbeson; Christopher L. Brummel; Roger Tung; Robert Silverman; Dario Doller
      Abstract: Publication date: Available online 9 November 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Julie F. Liu, Scott L. Harbeson, Christopher L. Brummel, Roger Tung, Robert Silverman, Dario Doller
      The use of deuterium substitution in an effort to produce kinetic isotope effects (KIEs) that favorably alter pharmacokinetics and metabolism in drug discovery has accelerated in the last decade. While the effects of deuteration remain highly experimentally determined and are unpredictable, an increasing number of deuterated drug candidates have progressed from early patent filings to successful proof-of-concept human studies, including the first FDA-approved deuterated drug. The scope of use of KIEs in drug design has expanded, and now deuteration of drug candidates and tool compounds, including imaging ligands, has become a welcome instrument in the arsenal of medicinal chemists. It is expected that experimentation with strategic introduction of deuterium into the structures of organic compounds will continue to increase and may enable the future development of a variety of novel drugs and chemical tools. In this chapter an update on the topic of deuterium substitution in medicinal chemistry will be provided, focusing on the diversity of ways in which medicinal chemists are using deuteration in their efforts to deliver better drugs.

      PubDate: 2017-11-11T11:48:43Z
      DOI: 10.1016/bs.armc.2017.08.010
       
  • DNA-Encoded Library Technology: A Brief Guide to Its Evolution and Impact
           on Drug Discovery
    • Authors: Robert A. Goodnow; Christopher P. Davie
      Abstract: Publication date: Available online 6 November 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Robert A. Goodnow, Christopher P. Davie
      In the 25 years since the first publication of the concept of encoded combinatorial library synthesis with sequences of DNA, DNA-encoded library technology (DELT) has become a widely accepted method for hit finding along with high-throughput screening. This method has been shown to be useful by the numerous, valuable hits that have been published as well as by the announcement of several drug development candidates that originated from DELT hits. Multiple methods exist for directing and encoding library synthesis, demonstrating the robust nature of this informational and functional platform. In its current, commonly practiced format, this method is in theory readily applicable to any hit finding problem for soluble protein targets. The robust nature of DNA binding and recognition properties is part of the continuous evolution of DNA-encoded and DNA-directed methods.

      PubDate: 2017-11-11T11:48:43Z
      DOI: 10.1016/bs.armc.2017.09.002
       
  • Free Energy Calculation Guided Virtual Screening of Synthetically Feasible
           Ligand R-Group and Scaffold Modifications: An Emerging Paradigm for Lead
           Optimization
    • Authors: Robert Abel; Sathesh Bhat
      Abstract: Publication date: Available online 26 October 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Robert Abel, Sathesh Bhat
      Virtual screening of small-molecule collections has become a widespread practice both in academic laboratories and in pharmaceutical companies to rapidly and inexpensively identify small molecules which bind to the intended target with sufficient affinity to facilitate initiation of a drug discovery project. However, this approach of computationally evaluating very large numbers of small molecules, and then selecting a small subset of these for additional experimental prosecution is seldom employed in the lead optimization phase of drug discovery project. Recent work enabling programmatic enumeration of the synthetically tractable idea space around the most promising lead molecules when appropriately combined with high-accuracy protein–ligand binding free energy calculations appears poised to allow this emerging paradigm to make great contributions to lead optimization.

      PubDate: 2017-11-05T10:52:00Z
      DOI: 10.1016/bs.armc.2017.08.007
       
  • Kinase-Centric Computational Drug Development
    • Authors: Albert J. Kooistra; Andrea Volkamer
      Abstract: Publication date: Available online 15 October 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Albert J. Kooistra, Andrea Volkamer
      Kinases are among the most studied drug targets in industry and academia, due to their involvement in a majority of cellular processes and, upon dysregulation, in a variety of diseases including cancer, inflammation, and autoimmune disorders. The high interest in this druggable protein family triggered the generation of a large pool of data comprising sequence, structure, bioactivity, and mutation data. Together with this continuously growing amount of available data, comes the need as well as the opportunity to organize, analyze, and utilize this data in order to aid the design of novel, active, and potentially selective kinase inhibitors. In this chapter, we provide a comprehensive overview of kinase-centric data resources and tools that can be utilized for computationally driven kinase research. The contents of all resources are summarized, and all platforms focused on human kinases are discussed in more detail. Furthermore, practical applications from literature and illustrative examples showcasing the aforementioned sources and tools are presented. These applications utilize sequence, structure, and bioactivity data and range from single structure analysis, sequence comparisons, binding site predictions, druggability predictions, and protein–ligand interaction fingerprinting to activity predictions using machine learning methods. Finally, a perspective is given on the unmet needs, potential pitfalls, and current developments in kinase drug design.

      PubDate: 2017-11-05T10:52:00Z
      DOI: 10.1016/bs.armc.2017.08.001
       
  • High-Throughput Screening
    • Authors: Mary Jo Wildey; Anders Haunso; Matthew Tudor; Maria Webb; Jonathan H. Connick
      Abstract: Publication date: Available online 15 October 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Mary Jo Wildey, Anders Haunso, Matthew Tudor, Maria Webb, Jonathan H. Connick
      This review provides an overview of the science of high-throughput screening (HTS) within the pharmaceutical industry and the greater drug discovery community. From its origins in the early 1990s to the current state of the art, key aspects of the process are introduced and described in increasing levels of detail. Examples of technologies employed in the automation of HTS are provided, together with an evaluation of their applicability and limitations. The various detection modalities typically encountered, and their suitability to high-density screening formats (96, 386, 1536, or 3456 well) are described. The increasing importance of informatics in screen design, data interpretation, quality control, and its contribution to the development of future HTS strategies is introduced. Current and future trends of how HTS is employed to meet the changing needs for new drug discovery are explored, including the parallel use of complementary screening modalities to sample diverse chemical matter and identify the best starting points for drug discovery programs.

      PubDate: 2017-11-05T10:52:00Z
      DOI: 10.1016/bs.armc.2017.08.004
       
  • CRISPR–Cas9 for Drug Discovery in Oncology
    • Authors: Sylvie M. Guichard
      Abstract: Publication date: Available online 13 October 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Sylvie M. Guichard
      Drug discovery is a complex enterprise bringing together a variety of skills and techniques. Oncology drug discovery has taken advantage of cancer genetics to identify drug molecules tailored to specific subset of tumors which has proven highly beneficial to patients. Modifying the genome to understand better cancer genetics has been instrumental in this process. CRISPR–Cas9 is a new programmable gene-editing tool which expand dramatically the scope of genetic manipulation to decipher cancer biology. CRISPR–Cas9 has taken drug discovery by storm and many facets of drug discovery could benefit from this technology. This chapter will briefly touch on the mechanism of genome editing and the growing number of modified Cas9 enzymes before presenting how CRISPR–Cas9 is impacting different aspects of drug discovery namely target identification, validation and deconvolution, reagent generation and drug synthesis, assessment of drug sensitivity and drug resistance, as well as drug disposition and toxicology.

      PubDate: 2017-10-14T14:31:54Z
      DOI: 10.1016/bs.armc.2017.08.006
       
  • Fragment-Based Lead Discovery
    • Authors: Ben J. Davis; Stephen D. Roughley
      Abstract: Publication date: Available online 12 October 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Ben J. Davis, Stephen D. Roughley
      Since its inception in the late 1990s, fragment-based lead discovery (FBLD) has developed into a robust and generic approach for drug discovery. Two clinically approved drugs have been developed using the FBLD approach, and at least 30 FBLD-derived compounds are in various stages of clinical development. Based on the principle of the identification of small (and hence typically low affinity) ligands which make well-defined interactions with the receptor, and the evolution of these initial fragment hits into larger, more potent ligands that maintain these key interactions, FBLD has proven to be a reliable technique which is applicable to wide range of targets. In this chapter, we will discuss the philosophy and rationale underpinning the FBLD approach, theoretical and practical considerations of fragment library design, fragment screening and characterization, and the evolution of initial low molecular weight fragment hits into larger, potent molecules suitable for lead optimization and preclinical development. We will also discuss informative case histories, showing the challenges, pitfalls, and successful approaches, which have been applied to a number of therapeutically relevant targets.

      PubDate: 2017-10-14T14:31:54Z
      DOI: 10.1016/bs.armc.2017.07.002
       
  • Targeted Protein Degradation
    • Authors: Nello Mainolfi; Tim Rasmusson
      Abstract: Publication date: Available online 9 October 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Nello Mainolfi, Tim Rasmusson
      Targeted protein degradation is arguably one of the most exciting novel therapeutic modalities in drug discovery. Moving away from occupancy-based pharmacology models and their challenges with selectivity, on/off target toxicities, and PK–PD limitations, it provides a novel and orthogonal therapeutic paradigm. The ability to induce degradation using a small molecule without the need to inhibit a specific protein function allows access to unexplored new areas of biology and targeting historically intractable protein targets. This chapter reviews the field especially focusing on heterobifunctional molecule-driven target degradation and highlights great progress but also gaps needed to be filled as the field moves toward clinical validation.

      PubDate: 2017-10-14T14:31:54Z
      DOI: 10.1016/bs.armc.2017.08.005
       
  • Platform Technologies in Drug Discovery and Target Validation
    • Authors: Amit Kumar; Jason White James Christie Nazzareno Dimasi Changshou Gao
      Abstract: Publication date: Available online 4 October 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Amit Kumar, Jason White, R. James Christie, Nazzareno Dimasi, Changshou Gao
      Antibody–drug conjugates (ADCs) are designed with the purpose of delivering small-molecule cytotoxic drug to antigen-expressing tumor cells by harnessing the specificity, biodistribution, and pharmacokinetics of antibodies. ADCs are comprised of three components: the antibody, the linker, and the cytotoxic agent. To achieve the desired goal of targeted therapy with anticipated efficacy and safety profiles, each ADC component must be carefully selected and optimized. In this chapter, we introduce the main concepts and technologies associated with clinical development of ADCs. Considerations regarding ADC production such as drug–antibody conjugation, linker technologies, and cytotoxic agents are discussed. In addition, we describe analytical methods to characterize ADC products for assessment of drug content and purity. Finally, mechanistic aspects ADCs in vivo and the underlying key factors effecting on- and off-target toxicities are introduced.

      PubDate: 2017-10-08T21:21:56Z
       
  • The Chemistry of Oligonucleotide Delivery
    • Authors: David B. Rozema
      Abstract: Publication date: Available online 13 September 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): David B. Rozema
      The field of oligonucleotide-based therapeutics has advanced through decades of research and development to identify diverse structures and mechanisms of action with the aim of using nucleic acids as drugs. Despite this diversity, there are common characteristics that all oligonucleotides require to be functional drugs: potency, stability against nucleases, and access to sites of activity. The aim of this review is to introduce the different types of nucleic acid therapeutics and the strategies for attaining the “drug-like” attributes required of membrane-impermeable nucleic acids.

      PubDate: 2017-09-17T18:37:40Z
      DOI: 10.1016/bs.armc.2017.07.003
       
  • Phenotypic Screening
    • Authors: Alleyn T. Plowright; Lauren Drowley
      Abstract: Publication date: Available online 4 September 2017
      Source:Annual Reports in Medicinal Chemistry
      Author(s): Alleyn T. Plowright, Lauren Drowley
      Phenotypic screening is now reestablished in academia and industry as an approach to discover novel drug targets, pathways, and high-quality hit and lead molecules. The increased access to patient-derived cells or tissues and developments in induced pluripotent stem cell technology coupled to more complex cellular systems such as three-dimensional cultures or organs on a chip is providing opportunities for more disease-relevant screens. Different modalities are available to screen including small molecules, siRNA, antibodies, and CRISPR libraries, and each offers a range of advantages and disadvantages. The size of the phenotypic screen can range from high-throughput screens to more hypothesis-based selections including biological measures of diversity. New approaches are now appearing based on the principles of fragment-based screening. One of the major challenges in phenotypic screening is the deconvolution of the biological target(s) of the hit molecules, but a range of methods based on computational techniques utilizing different sources of data can infer the possible targets to generate initial target hypotheses which can be tested. Even in the absence of biological target information, if the phenotypic assay is sufficiently robust, compounds can be optimized into lead molecules and even clinical candidates. The application of cross-disciplinary phenotypic discovery to probe emerging biology is a powerful and exciting approach to discover new biological targets and molecules and, as highlighted in this chapter, is making a significant impact on drug discovery and ultimately delivering transformative medicines to impact the lives of patients.

      PubDate: 2017-09-06T17:00:52Z
      DOI: 10.1016/bs.armc.2017.07.001
       
 
 
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