Lecture 1 Introduction to Drug Discovery

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

2. 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. Generally,a drug can be defined as a substance that induces a response within the human body. Dr. Abd El Raheim Donia

3. Drug discovery • 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. Drug Discovery: This process involves finding the target that causes or leads to the disease. Next, chemical or biological compoundsare screened using specific assays and are tested against these targets to find leading drug candidates for further development. Dr. Abd El Raheim Donia

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 AirbusA380 at US $ 270 million, or five times that of a Boeing B -787 at US $ 200 million. Dr. Abd El Raheim Donia

5. Drug Discovery Process Dr. Abd El Raheim Donia

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

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

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

9. Dr. Abd El Raheim Donia

10. Dr. Abd El Raheim Donia

11. History and Background of the use of Natural Products as Therapeutic Agents------------------------------------------------ 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 NeiChingis one of the earliest health science anthologies ever produced and dates back to the thirtieth century bc. Dr. Abd El Raheim Donia

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

13. The Chinese MateriaMedicahas 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 Donia

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

15. Authors of antiquity Hippocrates(460-377 BC)“The Father of Medicine” Dr. 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. • 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 PedaniousDioscorides in approximately ad 100 produced a work entitled De MateriaMedica, 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. Dr. Abd El Raheim Donia

17. The Arab World Dr. Abd El Raheim Donia

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 JirjisBakhtyishu’, 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

19. HunaynIbnIshaq 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

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

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

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

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

25. ARABIAN MEDICINE IN EUROPE Reference has already been made to the translation of al-Razi’sKitabal Mansurifi al-tibb, ibnSina’s al-Qanunand the 30th volume of al Zahrawi’sal-Tasrifinto 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. Dr. Abd El Raheim Donia

26. The 18thcentury • Johann Adam (1759-1809) • Linnaeus (naming and classifying plants) • At the end of the 18th century, crude drugs were still being used as powders, simple extracts. 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) Dr. Abd El Raheim Donia

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

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. Dr. Abd El Raheim Donia

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