1. Lecture 1 Introduction to Drug Discovery 1 Dr. Abd El Raheim Donia

2. Generally, a drug can be defined as a substance that induces a response within the human body. Dr. Abd El Raheim Donia2 FDA Definition of a Drug An active ingredient that is intended to induce pharmacological activity or other direct effect in the diagnosis, cure, treatment, or prevention of a disease.

3. Is the process of generating (compounds and data) and evaluating all of the necessary information to determine the feasibility of a new chemical entity (NCE) to become a safe and effective drug. Dr. Abd El Raheim Donia 3 Drug Discovery: This process involves finding the target that causes or leads to the disease. Next, chemical or biological compounds are screened using specific assays and are tested against these targets to find leading drug candidates for further development. Drug discovery

4. Total drug development time grew from an average of 8.1 years in the 1960s to 11.6 years in the 1970s, to 14.2 in the 1980s, to 15.3 years for drugs approved from 1990 through 1995. Another report in 2003 has put the figure at 11.8 years. The average cost of developing a new drug is estimated to be about US $ 1 – 1.2 billion, including expenditures on failed projects. This amount is about four times the price of an Airbus A380 at US $ 270 million, or five times that of a Boeing B -787 at US $ 200 million. DR. ABD EL RAHEIM DONIA 4

5. Drug Discovery Process 5 Dr. Abd El Raheim Donia

6. What is drug discovery ? Therapeutic Target Lead Discovery Lead Optimization Clinical Candidate Commercial Drug drug design

7. Working at the Intersection  Structural Biology  Biochemistry  Medicinal Chemistry  Toxicology  Pharmacology  Biophysical Chemistry  Information Technology

8. Drug Discovery & Development Identify disease Isolate protein involved in disease (2-5 years) Find a drug effective against disease protein (2-5 years) Preclinical testing (1-3 years) Formulation Human clinical trials (2-10 years) FDA approval (2-3 years)

9. Step Time (Years) Cost in million US$ Comments 1 Identify disease 2 Isolate protein (Mainly). 2-5 Identifying which proteins are responsible for the disease (e.g. by identifying genetic changes that can cause the disease). 3 Finding the drug2-5400 Involves searching for compounds that interacts with the target protein. 4 Pre-clinical test1-3 Testing on animals 5 Clinical Phase I1-2 First human tests for safety: 10-100 healthy persons. 9Dr. Abd El Raheim Donia

10. Step Time (Years) Cost in million US$ Comments 6Clinical Phase II1-2 Testing for safety and effectivity: 50-500 persons from the disease group. 7Clinical Phase III2-3500 Large scale efficiency test: 200-2000 persons (typically several hospitals in different demographic regions). 8FDA Approval1-2 Obtain the necessary governmental approvals for drugs. In America drugs must be approved by the US Food and Drug Administration. 9Post Approval (Phase IV) 100Monitoring long-term effect Extending use of the drug to different classes of patients (such as children) Finding new therapeutic opportunities. DR. ABD EL RAHEIM DONIA 10

11. Dr. Abd El Raheim Donia 11 Throughout the ages humans have relied on Nature to achieve basic needs as the production of foodstuffs, shelters, clothing, means of transportation, fertilizers, flavors and fragrances, and medicines. Nature has provided many things for humankind over the years, including the tools for the first attempts at therapeutic intervention. * The Nei Ching is one of the earliest health science anthologies ever produced and dates back to the thirtieth century bc.

12. *Some of the first records on the use of natural products in medicine were written on clay tablets and date to approximately 2600 bc. Indeed, many of these agents continue to exist in one form or another to this day as treatments for inflammation, influenza, coughing, and parasitic infestation. *Chinese herb guides document the use of herbaceous plants as far back in time as 2000 bc. DR. ABD EL RAHEIM DONIA 12

13. The Chinese Materia Medica has been repeatedly documented over centuries starting at about 1100 bc. Egyptians have been found to have documented uses of various herbs in 1500 bc. The best known of these documents is the Ebers Papyrus, which documents nearly 1000 different substances and formulations, most of which are plant-based medicines. Dr. Abd El Raheim Donia13

14. Egyptians (Ebers papyrus, 1550 BC) 14Dr. Abd El Raheim Donia

15. Authors of antiquity Hippocrates (460-377 BC)“The Father of Medicine” 15Dr. Abd El Raheim Donia

16. * A collection of Ayurvedic hymns in India from 1000 bc and earlier describes the uses of over 1000 different herbs. This work served as the basis for Tibetan Medicine translated from Sanskrit during the eighth century. Dr. Abd El Raheim Donia16 Theophrastus, a philosopher and natural scientist in approximately 300 bc, wrote a History of Plants in which he addressed the medicinal qualities of herbs and the ability to cultivate them. * The Greek botanist Pedanious Dioscorides in approximately ad 100 produced a work entitled De Materia Medica, which today is still a very well-known European document on the use of herbs in medicine. Galen (ad 130–200), practiced and taught pharmacy and medicine in Rome and published over two dozen books on his areas of interest. Galen was well-known for his complex formulations containing numerous and multiple ingredients.

17. The Arab World Dr. Abd El Raheim Donia 17

18. * The origins of Baghdad as the leading medical centre of the Muslim world in the ninth century. It has often been claimed that in the year 765 Jirjis Bakhtyishu’, the head of a prominent medical school in Jundishapur (situated about 300 miles to the south-east of Baghdad), was summoned to the capital to treat Caliph al-Mansur for dyspepsia. Dr. Abd El Raheim Donia 18

19. Hunayn Ibn Ishaq While translation of classical texts had already begun during the caliphate of Harun al-Rashid, it was boosted by the desire of his son Ma’mun to support the Mu’tazila clergy who were seeking a rational basis for Islamic belief that could challenge that of Christianity and other religions through the assimilation of acceptable ideas and opinions enunciated elsewhere. Dr. Abd El Raheim Donia 19

20. Abubakr Al Razi Among the greatest of the physicians who practised in Baghdad was Abu Bakr al-Razi, or, simply, al-Razi (known in the West as Rhazes), a Persian who died in the year 925. He was not only the director of a hospital in the city but was also an eminent philosopher and author of around 200 books on a diverse range of subjects. His medical writing included two major works, Kitab al-Mansuri fi al-tibb (The Book of Medicine for Mansur) and Kitab al-Hawi fi altibb (The Comprehensive Book on Medicine). Dr. Abd El Raheim Donia 20

21. Abu Ali Al-Hussain Ibn Abd allah Ibn Sina Another Persian philosopher who both practiced and wrote prolifically about medicine, namely Abu Ali al- Hussain ibn Abdallah ibn Sina (980–1037), generally known in the West as Avicenna. Dr. Abd El Raheim Donia 21

22. Ibn Sina (980-1037) ” القانون في الطب “ 22Dr. Abd El Raheim Donia

23. Ibn Albitar (1148-1197) ” الجامع لمفردات الأدوية والأغذية “ 23Dr. Abd El Raheim Donia

24. Abu Al-Qasim Al-Zaharawi It was not just in the East that Arabic culture thrived after the Muslim conquests. Under the enlightened rule of Abd-er- Rahaman III, Co´ rdoba, and in particular the suburb of the Umayyad royal palace, rivaled Baghdad in its grandeur until its conquest by the Berbers a century later. DR. ABD EL RAHEIM DONIA 24

25. Reference has already been made to the translation of al- Razi’s Kitab al Mansuri fi al-tibb, ibn Sina’s al-Qanun and the 30th volume of al Zahrawi’s al-Tasrif into Latin in the late twelfth century by Gerardo de Cremona. It was largely through the efforts of this prolific translator that Christian Europe obtained access to the major Arabic medical texts. ARABIAN MEDICINE IN EUROPE Dr. Abd El Raheim Donia 25

26. THE 18 TH CENTURY Johann Adam (1759-1809) Linnaeus (naming and classifying plants) At the end of the 18 th century, crude drugs were still being used as powders, simple extracts. Dr. Abd El Raheim Donia26 The era of pure compounds In 1803, a new era in the history of medicine Isolation of morphine from opium, Strychnine (1817) Quinine and caffeine (1820) Nicotine (1828) Atropine (1833) Cocaine (1855)

27. General Identifications ADME: Absorption, distribution, metabolism, and elimination. These are the defining pharmacokinetic characteristics of how a drug is handled by the body. Bioinformatics: The collection, organization and analysis of large amounts of biological data, using computers and databases. Bioinformatics also includes the integration of databases. Dr. Abd El Raheim Donia 27

28. In vitro: ”in glass.” Studies that are performed in test tubes, flasks, or multi well plates or any biological preparation that is not considered a living organism In vivo: ”in life.” Studies that are done in living microorganisms, animals, or humans. 28 Dr. Abd El Raheim Donia

29. Credit Hours: 1 (1 + 0) Level: 5 Course Evaluation: ▪ 1 st. Assessment Exam.: 20% ▪ 2 nd. Assessment Exam.: 20% ▪ Quizzes: 10% ▪ Performance: 10% ▪ Final Exam. : 40% ▪ Total: 100% Dr. Abd El Raheim Donia 29