1. Introduction

In early ages and still in some regions today, drug discovery is a form of alchemy. Pharmacists, botanists, and others who prepare medicines used various types of apparatus to separate the mixed substances, heating to different temperatures to distil off the more volatile materials. Liquids were poured from one container to another through a filter, in the hope that some solid residue would remain on the filter or in the original container. Mixing liquids together sometimes produced a solid material, which was collected and tested. When such unorganised and mainly empirical efforts produce a drug like quinine from the bark of the cinchona tree or morphine from the opium poppy, this is drug discovery, but it is a matter of luck rather than logic and science. The effects of quinine on malaria were discovered when the Countess of Chinchon was treated with a preparation of the bark in 1638, but it was the bitter taste which led the Peruvian Indians to chew the bark for the relief of shivering, thus indicating a useful substance with an unmistakable symptom. In the case of morphine, the effects of opium in various diseases were known and a number of alkaloids were extracted and tested. The realization that raw opium contained valuable medicinal ingredients was dramatically confirmed in an early application of the isolation and synthesis of a pure drug, using the knowledge of the time. The first step towards modern drug discovery, using an understanding of biology to give more logical and less empirical results, was the introduction of the scientific method in the 17th and 18th centuries, though this had little immediate impact on medical practice. Various chemical and botanical methods of extracting and testing drugs, often borrowed from established practices in the dye and poison industries, were developed and used to give an ever increasing number of new medicines. This trend was accelerated by new ideas in chemistry and medical theory. For the aforementioned example of the dye industry, a highly significant drug discovery came in 1853, when the active principle of the Chichona bark was isolated in crystalline form and named quinine by the French chemists Pelletier and Caventou, who were using the same methods to extract poisons and medicines from plants. Such chemical and structural analyses of drugs are considered as part of drug discovery in the drug metabolism and pharmaceutical chemistry field.

1.1. Definition of Drug Discovery

In order to understand methods by which disease treatment is discovered and developed, it is important to appreciate what we mean by the phrase “drug discovery.” A useful definition describes drug discovery as an integrated process of identifying a potential new medicine, from target identification through to product marketing. In other words, the aim of the drug discovery process is to find a compound or a group of compounds which can be developed into an effective medicine. This process can take 12 years or more and cost in excess of 1 billion dollars. However, this huge investment reflects the potential gain from developing a successful medicine. Drug discovery begins with an understanding of the disease to be treated or prevented. It involves the identification of a molecular target which plays a key role in the disease process. A molecular target is usually a protein and most drugs act by affecting the activity of a specific protein. The identification of a suitable target is an essential, influential step in the process. It is much less likely that a project will fail later in the process if a suitable target is identified early. The link between gene and disease is a key event in many pharmaceutical companies, and genetics is often the source of new projects and targets. Once a target is identified, a compound is sought which will affect the target and modulate its activity, with the ultimate aim of restoring the normal activity of the target and alleviating the disease. This compound can be a drug or a lead compound. However, it often takes modifications to the compound or the testing of many compound analogues to achieve a desirable effect. At this point, the term “compound” refers to it loosely and an effective drug may be developed from the active compound later in the process. The final stages of the process involve testing the new medicine in vitro and in vivo, before clinical trials with human subjects. These stages are costly and if the trial results are unfavorable, the whole project could be terminated.

1.2. Importance of Drug Discovery Techniques

In 1981, Wong and Gershon proposed the idea of effective drug discovery techniques in their study. According to their proposal, the development of world pharmaceutical sciences is categorized into traditional medicine, pharmaceutical chemistry, bio-pharmaceuticals, and now molecular medicine and genetic therapy. It has established the basic criteria of drug discovery technique. From ancient times, physicians have tried to cure diseases using new chemical entities. With the progress of technology and new investments, the world pharmaceutical industries are going ahead and expecting more advanced effective medicines. This needs more advanced drug discovery process. In recent years, in the era of genomics and computational biology, drug discovery is believed to be very different from the traditional small molecule drug method when compared to the complicated drug design process and development of medical biologicals. Modern drug discovery involves the identification of candidates, synthesis, characterization, screening, and assays for therapeutic efficacy. These techniques are hoping to improve the drug discovery success rates, lower the costs, and reduce the time to market. There are several reasons for the failure of drug discovery, development of ineffective drugs for patients. One of the reasons is due to the higher standards of proof of improved safety and efficacy from the government and the public in using drugs. In many cases, government regulatory agencies such as the US FDA have implemented tighter restrictions for the approval of new drugs. To market drugs and biologics, companies must provide evidence that the new compound is superior to other current therapies. This is a difficult task given that many major diseases such as cancer and autoimmune disorders have widely accepted treatments. Another reason can be the lack of understanding of the disease at the molecular level. It is now becoming known that many diseases thought to be related by their symptoms are actually different at the biological level. This is seen with the reclassification of certain cancers and discovery of diseases such as Alzheimer’s at the molecular level. This means that the disease is highly heterogeneous and can differ greatly from one patient to another. Failure to understand the disease at the molecular level has led to drugs that are effective for only a small subset of patients, or worse have had serious side effects due to the lack of specificity. High throughput drug discovery techniques are hoping to improve the drug discovery success rates.

2. Traditional Drug Discovery Techniques

2.1. Natural Product Screening

2.2. Target-Based Screening

2.3. Phenotypic Screening

3. Modern Drug Discovery Techniques

3.1. High-Throughput Screening

3.2. Combinatorial Chemistry

3.3. Computer-Aided Drug Design

4. Emerging Drug Discovery Techniques

4.1. Fragment-Based Drug Discovery

4.2. Virtual Screening

4.3. Artificial Intelligence in Drug Discovery

5. Challenges in Drug Discovery

5.1. Drug Resistance

5.2. Toxicity and Side Effects

5.3. Cost and Time Constraints

6. Future Directions in Drug Discovery

6.1. Personalized Medicine

6.2. Drug Repurposing

6.3. Nanotechnology in Drug Delivery