Frequently Asked Questions

Drug Discovery Basics

A "hit" is a chemical compound that produces a result in a preliminary biochemical test indicating that the compound merits further study as part of a drug discovery project. A "lead" is a compound that has been selected from a group of hit compounds based on qualities such as the intensity of the biochemical effect that occurs when the compound is present (efficacy), or the absence of coincidental effects (specificity). AsisChem's hit-to-lead service makes use of a systematic and iterative process to discover high-potency lead compounds with desired compound properties.

CRO's often claim that the purity of the compounds they synthesize and provide to their customers is "high," "very high," or even "unmatched." In practice, it rarely makes sense to test compounds of less than 98% purity due to the increasing likelihood of assigning inaccurate structure-activity relationship (SAR) data to compounds at lower levels of purity. AsisChem provides complete analytical documentation from standard, accepted methods for assessing compound purity, and can meet any purity specification required for productive experimentation.

The basic steps of pre-clinical drug development are:

• Drug target selection to identify a molecule or biochemical pathway to modulate in order to obtain the desired health effect
• Selection and acquisition of an appropriate compound library of thousands to millions of chemical compounds which may affect the drug target in some way
• Virtual screening (VS) and high-throughput screening (HTS) to identify compounds ("hits") that affect the drug target
• Secondary screening to confirm and characterize the hit compounds
• Analysis of screening data to select the best hits
• Iterative development, synthesis, and testing of hit compounds to optimize the assayed effect and other drug qualities
• Analysis of test data to select a lead compound for subsequent stages of drug development
• Development of efficient synthetic routes to create high-quality preparations of the lead compound in sufficient quantities for subsequent stages of drug development
• Pharmacological and pharmacokinetic studies using a variety of analytical biochemistry and animal testing (in vitro and in vivo) methods to determine the chemical properties and the absorption, distribution, metabolism, and excretion (ADME) profile of the lead compound
• Safety and toxicity studies to assess the risks of unwanted drug effects of the compound on major organs and organisms
• Formulation studies to determine how the compound interacts with various other compounds and materials required for drug manufacture, packaging, storage, and administration, such as tablet ingredients, coatings, carrier solutions, and medical tubing, and additional studies to determine how rapidly the compound breaks down under different storage conditions
• Development of additional new synthetic routes for safe, economical synthesis of greater quantities of the drug compound which will be needed for subsequent stages of drug development

Production of appropriate drug development documentation needed for regulatory filings and applications.

New chemical synthesis methods are required at several stages in drug development. Compound libraries used for high-throughput screening typically contain nanogram or microgram quantities of incompletely characterized compounds. Milligram quantities of lead compound are required for most pre-clinical development work. Clinical trials may require kilogram quantities. Once on the market, frequently prescribed drugs developed to treat large patient populations may require efficient synthesis of tons of purified drug compound.

"Drug discovery" refers to research activities leading up to the selection of a lead compound. Drug development encompasses pre-clinical and clinical research activities leading up to regulatory clearance to market a drug.

Researchers can avoid wasting drug development resource by analyzing the chemical structure of a potential lead compound for drug-like qualities. If the compound does not have structural properties consistent with good solubility in both aqueous and non-aqueous environments, it is not likely to be chosen for drug development. A "drug-like" compound is also small, and has additional structural features in common with safe, effective, approved, marketed drugs.

Medicinal chemistry describes the activities of pharmceutical researchers that identify, design, characterize, and synthesize drugs and potential drug compounds. Scientific disciplines practiced by medicinal chemists include organic and inorganic chemistry, biochemistry, cell biology, enzymology, pharmacology, bioinformatics, and cheminformatics.