Lead Compound Identification and Initial Optimization

Vocabulary flashcards covering lead compound identification, screening methods, small molecule sources, and drug pipeline stages from PHRX/PHAR 3005 Lecture 4.

Hit

An initial compound that demonstrates activity against a biological target in a single experiment, typically active at $1\text{--}20\,\mu\text{M}$.

Lead Compound

A validated hit compound that has demonstrated activity against a target across more than one experiment, typically active at $0.1\text{--}1\,\mu\text{M}$.

Drug Candidate

A compound optimized for potency ($0.01\text{--}0.001\,\mu\text{M}$), efficacy, and ADMET/PK properties necessary to function as a drug.

De Novo Drug Discovery

A drug discovery approach searching for compound(s) that modulate a target without prior structural knowledge of the active compound.

High-Throughput Screening (HTS)

A biochemical laboratory screening process testing large compound libraries (containing $1\text{,}000$ to $3\text{ million}$ compounds) against a target to discover active hits.

Virtual Screening

Computational screening of large chemical compound libraries to evaluate and predict potential biological activity.

Ligand-Based Virtual Screening (LBVS)

A virtual screening approach using key structural features (pharmacophore mapping) of known active small molecules as a model to identify similar compounds in databases.

Structure-Based Virtual Screening (SBVS)

A virtual screening method using computational simulations to dock compounds into a target binding site and score them based on fit.

Natural Products

Lead compound sources produced by living organisms, including plants, microorganisms, animals, and marine life.

Natural Ligands

Endogenous active molecules, such as neurotransmitters or enzyme substrates, utilized as structural starting points for drug design.

(S)-methacholine

A derivative of acetylcholine created by adding a single methyl group, which increases half-life and metabolic stability compared to acetylcholine.

'Me Too' Drugs (Follow-on Drugs)

New drugs designed by structural modification of existing drug classes (e.g., statins, penicillins) to create alternative options with optimized properties or improved binding.

Rational Design (Peptides)

A peptide drug discovery strategy that uses the known structure of a protein to design peptides capable of binding and disrupting protein-protein interactions (PPI).

Phage Display

A screening technique where bacteriophages displaying peptides, proteins, or antibodies on their surface are screened against a target antigen.

Mouse Hybridoma

An antibody identification technique in which mice are immunized with a target antigen to stimulate specific antibody production.

Discovery/Preclinical Stage Duration

The early phase of the drug discovery pipeline (including Target ID, Lead ID, Lead Optimization, and Preclinical Evaluation) lasting approximately $3\text{--}6\,\text{years}$.

Clinical Stage Duration

The development phase comprising Clinical Trials (Phase I-III) and FDA Review and Approval, lasting approximately $6\text{--}7\,\text{years}$.

IND Candidate

An investigational new drug candidate that has undergone lead optimization with potency around $\sim 0.01\,\mu\text{M}$ prior to final candidate selection.