Week 1 Trips 2026

Pharmaceutical sciences

A broad field focused on the design, development, and evaluation of drugs and pharmaceutical products; it includes chemistry, biology, pharmacology, clinical research, and health-systems research.

Molecular principle of drug action

A drug must recognize and bind its target to initiate the desired biological effect.

Drug

A chemical substance used to treat, cure, prevent, or diagnose disease, or to promote well-being.

Central challenge of drug development

Many properties must be optimized simultaneously, and improving one property may worsen another; success requires the best overall compromise.

Major properties optimized in drug development

Potency, efficacy, selectivity, toxicity, ADME, protein binding, stability, accessibility, cost, patentability, solubility, taste, and formulability.

Why develop a new drug?

Examples include no existing treatment, poor absorption, poor solubility, instability, rapid metabolism, lack of site selectivity, formulation problems, or poor patient acceptance.

Traditional integrated discovery structure

A large pharmaceutical company performs chemistry, biology, CADD, ADME, and other functions internally using an internal budget.

Distributed discovery structure

A small biotechnology company uses capital markets and multiple contract research organizations for chemistry, biology, CADD, ADME, and other work.

Translational research

An ongoing continuum in which basic discoveries move toward human health applications and clinical observations feed back to basic research.

T0 translational stage

Basic and applied research focused on identifying the right target, hits, leads, and candidate.

T1 translational stage

Translation to humans, including Phase 1 studies.

T2 translational stage

Translation to patients, including later clinical development.

T3 translational stage

Translation to practice, including postmarketing use and surveillance.

T4 translational stage

Translation to communities through population studies and outcomes research.

Nine steps from target to pill

Target identification, hit identification, hit-to-lead, lead optimization, IND-enabling studies, Phase 1, Phase 2, Phase 3, and FDA approval.

Drug discovery portion of the funnel

Target identification through lead optimization and IND-enabling preparation.

Drug development portion of the funnel

Clinical Phases 1 through 3, regulatory filing, and approval.

Attrition

Progressive loss of compounds or projects as increasingly demanding discovery and development criteria are applied.

Characteristics of a rigorous researcher

Curiosity, collaboration, communication, analytical thought and foresight, persistence, and flexibility.

FDA's simple top rule

Demonstrate safety and efficacy.

Three historical schools of drug discovery

Phenomenology, rationalism or mechanism-based discovery, and parallel processing.

Phenotypic screening

Identifies active compounds using cell or organism assays without requiring a predefined molecular target.

Target-based screening

Tests compounds in biochemical assays against a defined molecular target.

Key advantage of phenotypic screening

It has identified more first-in-class drugs with new mechanisms of action in the lecture comparison.

Druglikeness

The combination of molecular properties that makes a molecule suitable as a drug, such as moderate molecular weight and balanced lipophilicity and hydrophilicity.

Druggable target

Usually a protein or other macromolecule whose modulation produces a biological response without unacceptable toxicity.

Common drug target classes

GPCRs, kinases, proteases, protein interfaces, enzymes, receptors, DNA, and RNA.

Natural products in drug discovery

Natural products and their derivatives are important starting points for approved drugs.

Hit

A molecule with measurable and reproducible activity in a cell-free pharmacological screening test.

Lead

A substance with improved target affinity, potency, and sufficiently favorable biological properties to justify extensive optimization and evaluation.

Candidate drug

A novel compound with attractive in-vivo potency, selectivity, toxicology, pharmacodynamics, cross-species activity, freedom-to-operate, economic feasibility, and drug-like properties for consideration in human studies.

Hit expansion

Evaluation and exploration of related compounds to identify a tractable series with suitable activity and developability.

Ideal hit properties

Affinity, selectivity, cellular efficacy, druglikeness, metabolic stability, permeability, solubility, low cytotoxicity, synthetic tractability, and patentability.

Hit-to-lead objective

Demonstrate in-vitro tractability while improving potency, selectivity, and bioavailability.

Lead optimization

An iterative process of improving a lead and using advanced models to identify risks before clinical development.

DMTA cycle

Design, Make, Test, Analyze.

Structure-activity relationship or SAR

The relationship between chemical structure and biological activity; small structural changes can cause major changes in response.

Structure-property relationship

The relationship between chemical structure and physicochemical or developability properties such as solubility, permeability, and metabolism.

Pharmacokinetics or PK

What the body does to the drug, including absorption, distribution, metabolism, and elimination.

Pharmacodynamics or PD

What the drug does to the body, including target effects, efficacy, and toxicity.

ADME

Absorption, distribution, metabolism, and excretion or elimination.

Absorption

Movement of a drug from its administration site into the central compartment.

Distribution

Reversible transfer of a drug from one location to another within the body.

Metabolism

Chemical reactions that convert drugs into more polar compounds that can be eliminated.

Elimination

Processes that remove a drug from the body in unchanged or modified form.

Toxicity

The degree to which a substance may harm humans or animals.

Clearance, Cl

A pharmacokinetic measure describing removal of drug from the body.

Volume of distribution, V

A pharmacokinetic parameter relating the amount of drug in the body to its measured concentration.

Half-life, t1/2

The time associated with a drug concentration or amount decreasing by one half.

Bioavailability, F

The fraction of an administered dose that becomes available to the systemic circulation or target-relevant compartment.

Fundamental assumption of drug action

Biological effect is directly related to drug concentration at the site of action.

Factors reducing drug available to target

Insolubility, instability, metabolism, poor absorption, tight protein binding, binding to other macromolecules, poor distribution, and premature excretion.

Protein binding

Reversible binding of drug to plasma or tissue proteins; free drug competes for target binding, distribution, metabolism, and excretion.

Why protein-binding off-rate matters

Drug availability depends not only on the extent of binding but also on how quickly bound drug dissociates.

Passive membrane diffusion requirement

A drug needs a balanced ratio of lipid-solubilizing and water-solubilizing regions.

Goldilocks principle in solubility

A useful drug often needs balanced lipophilicity and hydrophilicity rather than an extreme of either.

Purpose of drug metabolism

Generally increases polarity to help eliminate lipophilic xenobiotics and prevent accumulation.

Possible outcomes of drug metabolism

Inactive to active, active to inactive, active to another active metabolite, active to toxic, or inactive to another inactive substance.

Reactive metabolite risk

A reactive metabolite may form covalent adducts with cellular proteins and produce toxicity.

Conjugation

Attachment of a drug or metabolite to another molecule, often supporting detoxification and elimination.

IND-enabling studies

Preclinical safety, toxicokinetic, formulation, and manufacturing studies intended to support initial testing in humans.

Typical IND-enabling safety design in the lecture

Safety testing in two species, acute and chronic toxicity evaluation, and multiple dose levels including a level that produces toxicity.

CMC

Chemistry, Manufacturing, and Controls activities supporting product identity, purity, stability, formulation, and reproducible manufacturing.

Phase 1 main focus

Human safety, tolerability, and intensive PK or PD characterization.

Single ascending dose study

Participants receive progressively higher single doses until a maximum or stopping criterion is reached.

Multiple ascending dose study

Participants receive repeated escalating doses to characterize safety and PK or PD.

Food-effect study

Evaluates how food changes drug absorption.

Phase 2 main focus

Safety and preliminary effectiveness in patients with the target disease, often using randomized controlled designs.

Phase 3 main focus

Large patient studies assessing effectiveness, adverse reactions, and superiority or non-inferiority versus existing treatment.

Superiority trial

Tests whether a new intervention performs better than the comparator.

Non-inferiority trial

Tests whether a new intervention is not unacceptably worse than the comparator by a prespecified margin.

NDA

New Drug Application, the formal US application requesting approval to market a new drug.

Core NDA demonstrations

Safety and effectiveness for intended use, favorable benefit-risk, appropriate labeling, and adequate manufacturing controls.

Phase 4

Postmarketing surveillance and research conducted after approval to assess real-world use, long-term effectiveness, quality of life, comparisons, and cost-effectiveness.

Common reasons clinical trials fail

PK or PD problems, differences between animals and humans, inadequate study design, poor dose selection, suboptimal assessment timing, weak efficacy metrics, or flawed analysis.

Four 'rights' for clinical success

Right target, right drug, right patient, and right dose.

Correlation

A numerical description of association between two variables; it does not by itself establish causation.

Regression

A method that models how an independent variable is numerically related to a dependent variable and can estimate one from the other.

Empirical model

A simple, descriptive model based on observed relationships.

Mechanistic model

A model incorporating a deeper explanation of the processes producing the observed relationship.

Mass spectrometry

A go-to analytical tool for metabolite identification and quantification.

Role of liquid chromatography before MS

Separates mixture components before mass analysis and metabolite detection.

LOD

Limit of Detection, the lowest amount that can be reliably distinguished from absence, though not necessarily quantified accurately.

LOQ

Limit of Quantification, the lowest amount that can be quantified with acceptable performance.

HLOQ

Upper or high limit of quantification, the highest concentration that can be quantified within the validated range.

Linear dynamic range

The concentration range over which analytical response is reliably proportional to analyte concentration.

Accuracy

Closeness of a measurement to the real or accepted value.

Precision

Closeness of repeated measurements to one another, reflected by their spread.

Bias

Systematic measurement error inherent in the measurement process.

Why metabolite identification matters

It supports assessment of excretion, stability, reactive metabolites, cross-species differences, toxicology, and circulating human metabolites.

Three Rs of animal research

Reduce, Refine, and Replace.

IACUC

Institutional Animal Care and Use Committee, which reviews and oversees animal-research protocols and compliance.

Three Belmont principles

Respect for persons, beneficence, and justice.

Respect for persons

Protect autonomy, treat people with courtesy and respect, and obtain informed consent.

Beneficence

Minimize risks and maximize benefits.

Justice

Use non-exploitative procedures and distribute research costs and benefits fairly.

IRB

Institutional Review Board, which reviews human-subject research protocols before initiation.

GLP goal

Consistency, reliability, uniformity, reproducibility, and quality of laboratory research.

GCP goal

Protection of the rights, safety, and welfare of human research participants while assuring data quality, reliability, and integrity.

GMP goal

Ensure manufacturing processes are rigorously defined and monitored so drugs are produced with appropriate quality and safety.