Drug Discovery and Development - WPMU DEV

1 Drug Discovery and Development UNDERSTANDING THE R&D PROCESS. This is a fantastic time to be doing drug Discovery . PROCESS. We have an incredible wealth of knowledge that has been generated over the past few years.. Thomas Hughes, , Novartis DRUG Discovery AND Development : Overview It is the mission of pharmaceutical research companies to take the path from understanding a disease to bringing a safe and effective new treatment to patients. Scientists work to piece together the basic causes of disease at the level of genes, proteins and cells. Out of this understanding emerge targets, which potential new drugs might be able to affect (see How Drugs Work: The Basics on p. 3). Researchers work to: validate these targets, discover the right molecule (potential drug) to interact with the target chosen, test the new compound in the lab and clinic for safety and efficacy and gain approval and get the new drug into the hands of doctors and patients.

2 This whole process takes an average of 10-15 years. P U T T I N G I T I N T O P E R S P E C T I V E 15 years It can take up to fifteen years to develop one new TV. medicine from the earliest stages of Discovery to the Jay Leno debuts as host of The Tonight Show. time it is available for treating patients. Many of the The last episode of The Cosby Show airs. drugs coming to the market in 2007 were in the early Ted Turner, founder of CNN, is Time Magazine's stages of Discovery fifteen years ago, in 1992. Man of the Year. OPEN TO: Review The Process Let's rewind the calendar to 1992 and take a look at Politics what else was happening fifteen years ago. Democrat Bill Clinton defeats incumbent World Events President George Bush and businessman H. Ross Perot. The Federal Republic of Yugoslavia, created in 1918, collapses as Europe officially recognizes the Sports republics of Croatia and Slovenia.

3 Andre Agassi wins Wimbledon. Signed by Canada, Mexico and the , the North The Washington Redskins defeat the Buffalo American Free Trade Agreement establishes the Bills in Super Bowl XXVI. world's largest trading bloc. Technology Top-Grossing Films The Internet Society is chartered, and 1,000,000. Aladdin host computers are connected in a network. The Home Alone 2: Lost in New York term "surfing the net" is coined as an increasing Batman Returns number of people begin exploring the online world. Compact discs surpass cassette tapes as the preferred medium for recorded music. 1. PROCESS. DRUG Discovery AND Development . For the first time in history, scientists are begin- It takes about 10-15 years to develop one These numbers defy imagination, but a deeper ning to understand the inner workings of human new medicine from the time it is discovered understanding of the R&D process can explain disease at the molecular level.

4 Recent advances in to when it is available for treating patients. why so many compounds don't make it and genomics, proteomics and computational power The average cost to research and develop each why it takes such a large, lengthy effort to get present new ways to understand illness. The task successful drug is estimated to be $800 million one medicine to patients. Success requires of discovering and developing safe and effective to $1 billion. This number includes the cost immense resources the best scientific minds, drugs is even more promising as our knowledge of the thousands of failures: For every 5,000- highly sophisticated technology and complex of disease increases. As scientists work to harness 10,000 compounds that enter the research and project management. It also takes persistence this knowledge , it is becoming an increasingly Development (R&D) pipeline, ultimately only and, sometimes, luck.

5 Ultimately, though, the challenging undertaking. one receives approval. process of drug Discovery brings hope and relief to millions of patients. This page is FPO only SEQUENCING THE HUMAN GENOME Why It's a Big Deal In 2001 the sequencing of the human genome Knowing all the genes, and the proteins they Eventually, scientists hope to discover new was completed. There are about 20,000-25,000 code for gives scientists a full catalogue of drugs that precisely and powerfully prevent human genes, made up of 3 billion individual options to consider as potential targets for and cure disease. The human genome holds base pairs, the units of DNA. Each gene codes new drugs. It will take time, though, to achieve incredible potential. for a protein and these proteins carry out all the potential benefits of this new knowledge . the functions of the body, laying out how it Although we have a list of all the genes, we grows and functions.

6 These proteins can also do not know how they all interact and which be involved in disease. are involved in which diseases. 1. T HE Discovery PROCESS INCLUDES ALL EARLY RESEARCH TO IDENTIFY A NEW DRUG CANDIDATE AND TESTING. IT IN THE LAB . T HE PROCESS TAKES APPROXIMATELY 3-6 YEARS . BY THE END , RESEARCHERS HOPE TO HAVE A. PROMISING CANDIDATE DRUG TO TEST IN PEOPLE . PUBLIC AND PRIVATE Collaborations THE Discovery PROCESS Modern drug Discovery is the product of cooperation. Many sectors contribute, par- ticularly in building the basic science foun- Pre- Discovery dations. Both public and private organiza- Understand the disease tions play unique but increasingly interde- pendent roles in translating basic research Before any potential new medicine can be discovered, scientists work into medicine. to understand the disease to be treated as well as possible, and to unravel the underlying cause of the condition.

7 They try to under- Major biopharmaceutical companies are stand how the genes are altered, how that affects the proteins they the primary source of R&D funding for encode and how those proteins interact with each other in living new medicines, both for projects in their cells, how those affected cells change the specific tissue they are in own laboratories as well as for research and finally how the disease affects the entire patient. This knowledge licensed from other sectors. is the basis for treating the problem. Smaller companies also drive innovation, Researchers from government, academia and industry all contribute conducting basic research, drug Discovery , to this knowledge base. However, even with new tools and insights, preclinical experiments and, in some this research takes many years of work and, too often, leads to frus- cases, clinical trials. trating dead ends.

8 And even if the research is successful, it will take many more years of work to turn this basic understanding of what The National Institutes of Health (NIH). causes a disease into a new treatment. provides leadership and funding support to universities, medical schools, research centers and other nonprofit institutions, and stimulates basic research and early- stage Development of technologies that enable further targeted drug Discovery Some ideas may just stay on paper forever, and Development . but others have a way forward to make it into a pill, into a bottle at the pharmacy.. Debra Luffer-Atlas, , Eli Lilly and Company 2 3. HOW DRUGS WORK the basics Target Identification Choose a molecule to target with a drug Once they have enough understanding of the underlying cause of a The cells in our bodies carry out complex disease, pharmaceutical researchers select a target for a potential molecular reactions to perform every new medicine.

9 A target is generally a single molecule, such as a gene function from digesting your lunch, or protein, which is involved in a particular disease. Even at this early to moving your finger, to regulating cell stage in drug Discovery it is critical that researchers pick a target that growth and transmitting thoughts in is drugable, , one that can potentially interact with and be your brain. One type of molecule inter- affected by a drug molecule. acts with another which, in turn, affects another, and so on down the line. These Target Validation cascades of molecular changes are called chemical pathways. Test the target and confirm its role in the disease After choosing a potential target, scientists must show that it actually In many different and extremely complex is involved in the disease and can be acted upon by a drug. Target ways, these pathways are involved in validation is crucial to help scientists avoid research paths that look disease.

10 A mistake in one reaction might promising, but ultimately lead to dead ends. Researchers demon- stop an important protein from being strate that a particular target is relevant to the disease being studied produced or lead to too much production. through complicated experiments in both living cells and in animal These molecular imbalances can have big models of disease. consequences. Maybe they will cause extra cells to grow like in cancer or per- Drug Discovery haps cause the person's body to not Find a promising molecule (a lead compound ). produce enough insulin like in diabetes. that could become a drug Drug molecules affect these pathways Armed with their understanding of the disease, scientists are ready by interacting with certain molecules to begin looking for a drug. They search for a molecule, or lead along the pathway, making them more compound, that may act on their target to alter the disease course.