Intro to drug discovery Flashcards
What is drug discovery, and how has it evolved?
Drug discovery identifies target molecules for future medicines, designs and synthesizes potential lead compounds, and screens for efficacy and toxicity. It has advanced with the “omics” revolution, computational tools, combinatorial chemistry, and high-throughput screening.
What is X-ray crystallography and its application in drug discovery?
X-ray crystallography is a technique that images molecules by analyzing X-ray diffraction patterns. It is used to determine atomic structures, especially for protein-ligand complexes, aiding in drug design by studying specific molecular interactions.
Why are hydrogen atoms invisible in X-ray structures?
Hydrogen atoms are invisible in X-ray structures because they have no electrons to interact with X-rays, which primarily scatter off electrons to produce diffraction patterns.
How has NMR spectroscopy contributed to drug discovery?
NMR spectroscopy, which probes atomic nuclei spin, helps determine molecular structure and interactions in protein-ligand complexes. It has been critical in the discovery of drugs like the BCL-2 inhibitor navitoclax for cancer treatment.
What is the role of Artificial Intelligence (AI) in drug discovery?
AI, such as DeepMind’s AlphaFold, predicts protein structures and assists in chemical synthesis, shortening the lengthy drug discovery process by enabling efficient predictions of biomolecular interactions and aiding in compound design.
How has mass spectrometry advanced drug discovery?
Mass spectrometry (MS), especially with MALDI-TOF and ESI, enables rapid analysis of biomolecules. In drug discovery, MS aids in target validation, disease mechanism elucidation, biomarker identification, and studies of compound-protein interactions.
What is “open science” in drug discovery, and why is it important?
Open science in drug discovery involves freely sharing research outputs, such as raw data and resources, to reduce duplication, facilitate collaboration, and redirect efforts toward neglected or high-risk areas. Notable initiatives include the Structural Genomics Consortium and Drugs for Neglected Diseases Initiative.
Why is genetic diversity important in drug discovery?
Genetic diversity affects disease risk and drug response across populations. For instance, IL28B polymorphisms influence HCV drug efficacy among individuals of African descent, highlighting the need for diverse genetic representation in clinical trials.
Name three scientists and their contributions to drug discovery.
1) Gertrude Elion - discovered diaminopurine as a lead for cancer and antibacterial drugs, 2) James Black - pioneered receptor subtype targeting, leading to selective drugs, 3) Akira Endo - developed the first statin after screening fungi for HMG CoA reductase inhibitors.
What is the significance of inclusivity and diversity in drug discovery?
Inclusivity in drug discovery ensures diverse population representation, which improves drug safety and efficacy across different genetic backgrounds. It acknowledges variations in drug metabolism, disease susceptibility, and treatment outcomes.
