Drug discovery is the process by which new candidate drugs are discovered in the fields of medicine, biotechnology, and pharmacology. Drugs have historically been discovered by identifying the active ingredient from traditional remedies or by serendipitous discovery. In intact cells or entire species, chemical libraries of synthetic small molecules, natural products, or extracts were tested to classify compounds that have a beneficial therapeutic impact in a method known as classical pharmacology. Since human genome sequencing has permitted the rapid cloning and synthesis of large amounts of pure proteins, it has become standard practice to use high-performance screening of large compound libraries against isolated biological targets that are suspected as altering disease in a method known as reverse pharmacology. More recently, scientists have been able to understand and use this information to construct biological molecules at the atomic level.
Modern drug research requires the identification of screening hits, medicinal chemistry, and alteration of those hits to enhance susceptibility, selectivity (to minimize the risk for side effects), efficacy/power, metabolic stability (to optimize half-life), and oral bioavailability. If a compound has been developed that satisfies all of these requirements, before clinical trials, the drug development process can begin. Computer-aided drug design can be one or more of those steps, but not necessarily.
Drug research continues a lengthy, “costly, complex and inefficient process” with low rates of new clinical research, amid improvements in technology and understanding of biological processes. Drug discovery is carried out, with academic scientific support, by pharmaceutical companies. The ‘final product’ of the drug discovery is a patent on the new drug. In Phase I, II, and III, the drug requires very costly clinical trials and most fail. Small firms play a vital role, frequently selling the rights to bigger corporations with the money to operate the clinical trials.
The theory that the function of a drug in the human body is regulated by unique drug molecule interactions with biological macromolecules (mostly proteins or nucleic acids) prompted scientists to believe that the drug’s biological function involves individual chemicals. This made pharmacology towards the advent of the new period when pure chemicals became the mainstream medicines instead of simple extracts of medicinal plants. Examples of drug compounds derived from raw materials are morphine, the opioid active agent, and digoxin, a heart-stimulant from Digitalis lanata. Organic chemistry has contributed to the synthesis of much of the chemically derived natural products.
Substances, whether crude extracts or purified chemicals have historically been screened for biological activity without knowledge of the biological target. An attempt to identify the target was made only after an active agent had been detected. Its method is known as classical pharmacology, forward pharmacology, or the study of phenotypic drugs. The method of discovering a potential drug against a specified target for a specific disease typically requires high-throughput screening (HTS), in which large chemical libraries are tested for their ability to alter the target. Within the pharmaceutical industry, a “target” is produced. In general, the “target” is the naturally occurring cellular or molecular structure involved in the pathology of interest where the drug-in-development is supposed to act.
Traditionally, many medicines and other biologically active chemicals have been identified by the study of chemicals that organisms produce to influence the behavior of other species for survival. Despite the emergence of combinatorial chemistry as an important part of the lead discovery process, natural products still play a major role in drug development as the starting material[.
When a medication is developed with data throughout its trial history to prove it is safe and effective for the intended use in the United States, the manufacturer can request the New Medication Application (NDA) – for the drug to be marketed and approved for clinical use.