Requirements for a lead compound to become a clinical candidate

Franz F Hefti

doi:10.1186/1471-2202-9-s3-s7

Abstract

A drug candidate suitable for clinical testing is expected to bind selectively to the receptor site on the target, to elicit the desired functional response of the target molecule, and to have adequate bioavailability and biodistribution to elicit the desired responses in animals and humans; it must also pass formal toxicity evaluation in animals. The path from lead to clinical drug candidate represents the most idiosyncratic segment of drug discovery and development. Each program is unique and setbacks are common, making it difficult to predict accurately the duration or costs of this segment. Because of incidents of unpredicted human toxicity seen in recent years, the regulatory agencies and public demands for safety of new drug candidates have become very strict, and safety issues are dominant when identifying a clinical drug candidate.

Highlights

Because of incidents of unpredicted human toxicity seen in recent years, the regulatory agencies and public demands for safety of new drug candidates have become very strict, and safety issues are dominant when identifying a clinical drug candidate
Modern drug discovery and development efforts typically emerge from basic research and gradually move on to specific sequential tasks, which – if successful – culminate in a new drug for the treatment of a human disease
The overall pathway is structured by well-delineated milestones, which include selection of the drug target, identification of a lead compound, its modification to a compound suitable for toxicity testing in animals, and selection as drug candidate for clinical testing

Summary

Introduction

Modern drug discovery and development efforts typically emerge from basic research and gradually move on to specific sequential tasks, which – if successful – culminate in a new drug for the treatment of a human disease. From lead molecule to a drug candidate suitable for testing in formal animal toxicity studies. A molecule must satisfy basic needs of future manufacturing and storage It has to produce the desired pharmacologic effects on the target and in animal models of the disease, with a route of administration and frequency of dosing commensurate with practical use in humans. Failure of a drug candidate in toxicity testing may set a program back by several months if not years, because new analogs without toxicity must be identified To minimize this risk, experienced pharmaceutical companies typically generate several backup compounds in each medicinal chemistry program, with the hope that one among them will be devoid of toxicity. Patient safety is the absolute and primary concern in drug discovery and development, and the medical oath of not doing harm applies just as rigorously for participating drug discovery researchers

Conclusion

Bajorath J

Hefti FF