Drug Discovery Online Resources
AlphaFold is an artificial intelligence (AI) computational tool for predicting protein structure from sequence information. The associated protein structure database, AlphaFold DB, contains more than 200 million predicted protein structures as of 2023. AlphaFold is valuable to drug discovery because it provides structural information when experimental structural information is not available.
The Antibody Society website is a comprehensive platform offering information, updates, and educational materials in the field of antibody research. The associated section on approved or in-review antibody therapeutics is particularly valuable and allows readers to follow the evolving landscape of antibody therapeutics.
BindingDB is a database featuring more than a million measured binding affinities for interactions between compounds and proteins identified as potential drug targets. It supports drug discovery and medicinal chemistry through literature awareness, the development of structure-activity relationships, and validation of computational chemistry methods, making it a valuable drug discovery resource.
The BRENDA database compiles molecular and biochemical information about enzymes, including information about enzyme substrates and inhibitors. The database conveniently includes links to other resources, for example the PDB and Uniprot. BRENDA supports the exploration of biochemical pathways and facilitates drug discovery efforts focused on enzyme targets.
Cambridge Structural Database (CSD)
The Cambridge Structural Database (CSD) is a repository of experimentally determined structures of small molecules, boasting over a million curated entries. As an integral part of crystallographic databases, including the Protein Data Bank (PDB), the CSD facilitates the exploration of small molecule structures, supporting drug discovery efforts.
Chemical Abstracts Service (CAS)
CAS is a comprehensive database for chemical information, including literature references and compound properties, among others. CAS contains several resources, including CAS Registry, which holds information about compounds and proteins, and CAS References, containing bibliographic information from thousands of scientific journals.
ChemSpider is a freely accessible chemical structure database, offering access to over 100 million chemical structures. It's a valuable resource for exploring compounds and their properties, serving as a useful tool for drug discovery scientists.
ChEBI, or Chemical Entities of Biological Interest, stands as a chemical database focusing on small molecule entities. ChEBI classifies small molecules into groups and classes of entities. ChEBI provides valuable information on distinct compounds, aiding in understanding their bioactivity.
ChEMBL is a comprehensive database focusing on drug-like compounds with biological activity. Maintained by the European Bioinformatics Institute, it contains 2.4 million entries as of 2023. The database provides activity, assay, and target information, making it a potentially invaluable resource for drug discovery.
DrugBank is a practical and informative website for pharmaceutical research, offering detailed information on drug compounds and their targets in a user-friendly format. It is a convenient database for exploring drug properties and mechanisms, aiding in drug discovery and development decision-making.
European Medicines Agency (EMA)
Similar to the United States Food and Drug Administration (FDA), the EMA website provides regulatory information, drug approvals, and guidelines. Including both FDA and EMA resources can provide a more comprehensive view of global regulatory practices.
FDA Orange Book is a resource for approved drug products, generics, patents, and therapeutic equivalence evaluations. The resource also helps understand regulatory aspects.
GPCRDB, a comprehensive database, focuses on G Protein-Coupled Receptors (GPCRs), providing curated and annotated information for scientists, including those in drug discovery. It aids in the exploration and understanding of GPCR structures, functions, and ligand interactions, offering valuable insights for pharmacological research and drug development.
The Human Protein Atlas is a resource offering broad information on the expression and localization of human proteins in various tissues and organs and in healthy and diseased states. Conveniently, the website also provides structural and sequence information via links to the PDB and Uniprot.
National Institute of Health’s Chemical Information Database (PubChem)
PubChem is a straightforward resource for chemical information, providing a user-friendly platform to explore compounds and their properties and biological activities. The database can be a valuable tool in drug discovery and development.
National Institute of Health’s Clinical Trials Database
ClinicalTrials.gov, maintained by the NIH, is an extensive resource offering information on ongoing and completed clinical trials. This database enables exploration of clinical trials, their objectives, and outcomes, providing valuable insights for scientists, healthcare professionals, and patients.
Open Targets is a platform integrating genetic, genomic, and pharmacological data to aid in drug target identification and prioritization. It serves as a collaborative resource for researchers involved in early drug discovery.
Pharmacogenomics Knowledge Base (PharmGKB)
PharmGKB focuses on the impact of genetic variations on drug response. It aims to help scientists understand how genetic differences can impact an individual's response to a drug and how the genetic background influence drugs’ safety and efficacy.
The PDB serves as a central database for protein structural information, primarily obtained through X-ray crystallography. It contains information about proteins and their complexes with other biological macromolecules and with small molecules, including drugs. The PDB is an invaluable resource in structural biology, often used by drug discovery scientists for insights into protein structures and their interactions with compounds.
PKIDB, a curated and annotated database, serves as an up-to-date resource on protein kinase inhibitors currently in clinical trials, offering information for researchers and clinicians involved in drug development and therapeutic decision-making.Top of Form
United States Food and Drug Administration (FDA)
The FDA website is an essential source for drug discovery and development, providing valuable information on regulatory guidelines, approvals, and safety. This comprehensive repository covers drug evaluation, clinical trials, and regulatory compliance, allowing readers to stay informed on the latest approvals and breakthroughs.
UniProt is a public database that provides detailed information on proteins. It summarizes information about protein sequence, function, and known interactions. Importantly it also provides structural information by listing available structures from the PBD.
Drug Discovery Books
Basic Principles of Drug Discovery and Development by Benjamin E. Blass explains key concepts and principles of drug discovery and development and meticulously guides the reader through the entire process, from identifying targets to post-marketing surveillance, while providing examples for failed and successful drugs.
Starting with an overview in Chapter 1, the book delineates the two main phases: discovery, involving target selection and lead compound identification, and development, focusing on clinical utility through trials.
Chapter 2 delves into the historical evolution of drug discovery, exploring shifts in scientific understanding and overviewing milestones in drug discovery and regulatory practices.
Chapter 3 explores traditional drug targets, categorizing them based on function and structure, revealing the four major classes of drug targets–enzymes, G protein-coupled receptors, ion channels, and transporters–and overviewing new emerging target classes.
Chapter 4 explores in vitro and high-throughput screening in modern drug discovery, emphasizing their central role in discovering promising compounds that could become drug candidates. The chapter introduces the basic terms in screening and the different types of screening assays and formats.
Chapter 5 focuses on medicinal chemistry, outlining the iterative process of preparing and testing compounds to improve lead compounds' characteristics in drug discovery programs through structure–activity relationships (SAR).
Chapter 6 explores the role of absorption, distribution, metabolism, excretion (ADME), and in vivo pharmacokinetics in evaluating candidate compounds for their suitability in achieving the desired physiological response. The chapter emphasizes how these assessments guide the design of improved analogs and dosing levels for efficacy studies.
Chapter 7 explains the importance of animal models in drug development, emphasizing the need to demonstrate in vivo efficacy in relevant models. The chapter explores the diversity of available models and the impact of transgenic technologies on expanding the range of available models.
Chapter 8 explains the importance of safety in determining the clinical viability of a candidate compound, focusing on understanding how the compound interacts with biomolecules and building structure-activity relationships to minimize undesired effects. The chapter acknowledges the challenge of eliminating all safety risks, emphasizing the assessment of the therapeutic index to gauge the relative risk and enhance overall efficiency in the drug discovery process.
Chapter 9 delves into the fundamentals of clinical trials, stressing the need to assess clinical efficacy and safety before obtaining marketing authorization. The chapter outlines the key considerations in human clinical trials and explains the phased approach from safety-focused Phase I trials to efficacy-driven Phase III trial and post-marketing surveillance.
Chapter 10 explores translational medicine and biomarkers, responding to the escalating costs of drug development by bridging clinical observations and laboratory discoveries. The chapter overviews the fields' efforts to expedite drug discovery and development, emphasizing the collaboration between scientific knowledge and practical application.
Chapter 11 explains the organizational landscape and trends in the pharmaceutical industry, underscoring the importance of a well-structured approach that facilitates both scientific collaboration and business success. The chapter outlines common elements in institutions dedicated to introducing new drugs to the market and emphasizes the impact of industry trends and macroeconomic factors on the pursuit of next-generation therapeutics.
Chapter 13 provides case studies from successful and failed drug discovery programs, offering valuable lessons for those navigating the pharmaceutical industry.