Drug Discovery and Development Processes

Drug Discovery and Development Processes INTRODUCTION The human body is a miracle but it is also extremely vulnerable. Many illnesses and disorders are still untreatable. Fortunately science is always evolving. It is unravelling more and more secrets about how our body works and which process is occurring in conditions of sickness or health. The challenge is to use our scientific knowledge to discover new, innovative drugs, a new hope for the patients all over the world. Drug Designing or Drug Discovery and Development is an inventive process of finding new medications based on understanding of the biological target. Vast majority of drugs are small molecules designed to bind, interact and modulate the activity of specific biological proteins. These proteins which may also be receptors bind to and interact with other molecules to perform the numerous functions required for the maintenance of life. In many illnesses, one or more proteins or receptors in the body are not working correctly. That is what the scientists try to detect. If they discover which proteins or receptors cause an illness then these same proteins become the target for the development of a new drug. Thus, the target is the naturally existing cellular or molecular structure involved in the pathology of interest that the drug-in-development is meant to act on. Drugs work by interacting with target molecules (receptors) in our bodies and altering their activities in a way that is benef icial to our health. In some cases, the effect of a drug is to stimulate the activity of its targets (an agonist) while in other cases the drug blocks the activity of its target (an antagonist). DRUG DISCOVERY PROGRAMME A drug discovery programme initiates because of a disease or a clinical condition for which a suitable medical product is not available. It is this unmet clinical need which is the underlying driving motivation for the project. Developing a drug from an original idea to the launch of the finished product is a very labor-intensive, time consuming and expensive procedure which can take over 14 years to complete. Target-based drug discovery starts with a thorough understanding of the disease mechanism and the role of enzymes, receptors or proteins within the disease pathology. The initial research would include experimental procedures to identify proteins responsible of the disease and generation a hypothesis that the inhibition or activation of those protein or pathway will result in a therapeutic effect in a disease state. The outcome is the selection of a target which may require further validation prior to progression into the lead discovery phase in order to justify a drug discovery effort. During lead discovery an intensive search ensues with the help of a technique called High Throughput Screening (HTS) to find a drug-like molecule or biological therapeutic, typically termed as a development candidate, that will progress into the preclinical, and if successful, into clinical development and ultimately be a marketed medicine. Drug discovery process from target identification and validation through to filing of a compound and the approximate timescale for these processes. FDA: Food and Drug Administration; IND: Investigational New Drug; NDA: New Drug Application. DRUG TARGETS One of the most important steps in developing a new drug is target identification and validation. A target is a broad term which can be applied to a range of biological entities such as proteins, genes and RNA. A drug target is a key molecule involved in a particular metabolic or signal transduction pathway that is specific to a disease condition or a specific disease. Knowing the cellular targets of drugs is crucial if the process of drug discovery is to be made more efficient. Identifying the full spectrum of targets associated with a bioactive small molecule can lead to faster optimization, understanding of off-target side effects and the ability to minimize possible toxicities early on in the process. It is vital to have as much evidence as possible to support a target of choice before investing more resources in the target. Good targets share several features: involvement in a crucial biological pathway; distinction from any previously known target; functionally and structurally characterized; and druggable. A ‘druggable’ target is accessible to the putative drug molecule and upon binding elicits a biological response which can be measured both in vitro and in vivo. It also needs to be efficacious, safe, meet clinical and commercial needs. When searching for novel drug targets, candidates can be assessed according to how many of these features they have, as well as participation in a biological process critical to the disease. Identification of the target is followed by its validation which a process of physiologically, pathologically and pharmacologically evaluating a biomolecule. It might be performed at the molecular, cellular or whole animal level. The potential drug target is then subject to high-throughput screening against a library of drug-like compounds or to rational drug designin g. However, the term ‘drug target’ itself has several limitations. The following points should be kept in mind: First, a drug is disease-dependent, that is, every target is involved in a spectrum of diseases. Second, most human diseases are rather complicated and involve a number of risk factors, so there clearly are many different targets with respect to a specific disease. Targeting a specific target could not conceivably cure a disease. Third, there are many drugs targets the same target and one drug may have more than one target. The relationship between a drug and its target is not one-to-one but many-to-one. According to whether there are drugs available, a drug target can be classified into two classes: established drug targets and potential drug targets. The former are those for which there a good scientific understanding, supported by a lengthy publication history regarding both how the target functions in normal physiology and how it is involved in human pathology. Furthermore, there are many drugs targeting this target. The latter are those biomolecules whose functions are not fully understood and which lack drugs targeting them. Potential targets suggest directions for complete new drug research. At present, the most frequent protein targets for which successful drugs have been developed include proteases, kinases, GPCRs and nuclear hormone receptors. GPCRs and enzymes represent the most important classes of proteins for drug discovery. According to the DrugBank database, there are 435 effect-mediating drug targets in human genome. These structures are targets of 989 unique drugs, through 2,242 drug-target interactions. The dataset shows that receptors make up the largest group of drug targets: 193 proteins (44%) of the human drug targets) are receptors, and 82 (19%) of these are G protein-coupled receptors (GPCRs). In overall dataset, ~36% of drug targets are GPCRs. Ligand-gated ion channels are second largest receptor target class followed by receptor tyrosine kinases at the third place. Enzymes are the second largest group of target proteins in the human genome, comprising 29% of all human drug targets. Hydrolases are the most common class of enzymatic drug targets, comprising 49% of all human enzyme drug targets followed by oxidoreductases and transferases comprising 27% and 19% respectively. In addition, the majority (78%) of the enzyme targets are soluble proteins and not membrane-associated proteins. E.g.; cyclooxygenase 1 and cyclooxygenase 2, which belong to the oxidoreductase family are targeted by acetylsalicylic acid (aspirin).

Cell Bio Lab Report Essay

The purpose of this lab was to test the biological activity of ConA by performing a hemagglutination assay. If ConA is active then agglutination will occur due to ConA’s free receptors being able to bind to the glucose residues on the sheep’s red blood cells. If ConA is not active then no agglutination will occur. To test the hemagglutination reaction, two types of ConA solutions were compared, a purchased control ConA solution in buffer as the positive control, and a purified solution of ConA in buffer previously purified in lab. Each solution was at a 2mg/ml concentration of ConA in ConA buffer, which is necessary for ConA’s biological activity. Two variables were added, Galactose and Mannose, to the ConA solution to compare the effects each had on the hemagglutination reaction. I hypothesize for ConA to be able to agglutinate the red blood cells if in the adequate concentration and if in the presence of Galactose, not Mannose. Mannose will inhibit the ConA fro m binding to the red blood cell’s membrane, preventing agglutination. RESULTS The reaction plate containing the ConA dilutions was incubated over the weekend and resulted in all wells being pink, appearing as if every well had agglutinated. There was a vague outline of the non-agglutinated cells in various wells. The last agglutination was observed at titer 0.0625 (1/16). Agglutination was seen in rows A, B D, and E (row A contained the control ConA, row B contained the control ConA + Galactose, row D contained the sample ConA, and row E contained the sample ConA + Galactose). In the well rows C and F which contained control ConA + Mannose and sample ConA + Mannose, agglutination did not occur at any concentration of ConA. Row G, the negative control appeared to have agglutinated as well as Row H, which contained only ConA buffer. DISCUSSION AND CONCLUSION The results did not support my hypothesis for the biological activity of ConA. There are some sources of error that could explain the results obtained. It’s possible there was a problem with either the ConA buffer or the sheep red blood cells to allow for all wells to turn pink and appear agglutinated. Another explanation of the irregular results was there might have been cross contamination from not changing tips when transferring to different ConA concentrations, or if bubbles were introduced while diluting the ConA, making the results difficult to interpret. For wells A, B D, and E as ConA became more diluted or decreased in concentration, it became more difficult for it to effectively crosslink and agglutinate the red blood cells. Well D, the positive control that contained the purchased ConA resulted in agglutination of the first couple wells, then no agglutination as the ConA concentration decreased, similar to Row A. Wells B and E that had the Galacatose additive obtained the same titer of the control ConA because ConA does not bind Galactose. Galactose doesn’t interfere with ConA from binding to the sugar residues on the red blood cells. Mannose on the other hand, is an inhibitor to ConA’s binding sites. The Mannose in solution competed with the ConA and did not allow to bind to the sugar residues on the red blood cells as seen in rows C and F. Row G, the negative control, should have resulted in non-agglutination, similar to the rows containing the Mannose additive. The results observed showed agglutination formed in this row. Lastly, Row H should have shown non-agglutination through out because the well contained only ConA buffer, not ConA protein. In conclusion, the results did not clearly explain the biological activity of ConA with the hemagglutination assay. The experiment contained too many anomalies to get a clear determination of ConA’s functionality post purification. The results did show that a change in the concentration of ConA would alter the strength of the reaction. Also, ConA’s ability to bind to sugar residues can be affected if ConA has to compete or is inhibited to bind to a cells membrane. LITERATURE CITED Cell Biology 3822 Lab Manual, Cell Surface Glycoprotein Receptor Analysis Using Concanavalin A Lab 7. Pearson Learning Solutions. 2012: 147-154. Madeleine Zaechringer. Cell Biology 3822 Analysis of purified ConA via Hemagglutinatino Assay Lab 7: Powerpoint. 2014.

Behavioral Finance

Behavioral finance is a study which involves the influence of psychology on the attitudes and behavior of investors and its subsequent effects on the markets. Behavioral Studies is still in its development stages, but it is instrumental in determining/ explaining as to why or how markets might be inefficient. The difference between traditional finance and behavioral finance is that traditional finance is based on the following concepts: – Investors have rational behavior – Capital Asset Pricing Model (CAPM) – Markets are efficientBehavioral finance on the other hand says that, the psychological forces interfere with these concepts. It says that there are both internal and external behavioral obstacles towards the value creation of any company. In practical terms it brings forward the errors in judgments made by both individual investors and fund managers and the various biases to which we as humans are prone. Analyzing this will place us in a position to make dec isions which avoid errors/mistakes committed in the past . INVESTORS: Individual investors: An individual investor is a person who purchases small amounts of securities for him/herself.He is not professionally involved in investment services and whatever purchases he/she makes are on an arm’s length basis. Individual investors are highly regulated because they are thought of as amateurs with little or no knowledge. An individual investor is also known as retail investor or small investor . Professional investor: These investors are usually all those businesses which are involved in giving investment services either directly or indirectly for example, investment companies, mutual funds, investment banks, brokerage houses etc.Besides them professional investors could also be individuals which are professionally involved in giving investment services. Professional investors are also known as institutional investors. These investors are subject to fewer regulations probably becau se they are perceived as having superior knowledge to individual investors . Behavioral biases: Individual and Institutional investors are both prone to almost similar biases, because institutional investors are although organizations in their own right but in actual are lead by a handful of managers.Proponents of this study argue that humans are prone to bias in making their judgments no matter how qualified or experienced they may be. They say that humans make frequent use of heuristics, mental shortcuts/rules of thumb to simplify decisions and tasks that are complex. Availability heuristic: With availability heuristic it is believed that for humans the probability of an event occurring is dependent on how easily one can imagine that event happening. The more clear is the image the greater the probability.A related concept is Illusory correlation which describes we imagine and hence interpret evidence. Although this bias is limited for retail investors since not only their investm ents are smaller but they also don’t have various charts, patterns analyzing past year data at their disposal, as for institutional investors this bias is at a much more magnified level because many fund managers use charts and technical analysis which according to them helps in identifying various patterns and price/stock moments . Representativeness heuristic:This concept says that humans are prone making judgments that involve consideration of stereo-types instead of the underlying features. For example, while hiring the selection process takes into consideration the qualifications, relevant experience, personality etc. however this in no way can predict the future job performance of the individual. This also incorporates a related concept called Illusion of validity which puts forward that the confidence in one’s judgment is primarily based on the representation of the situation instead of the characteristics.However, retail investors are more prone to this bias as compared to institutional investors because they have the information that is available to the general public for example, commentaries from financial journalists, analysts which believe that well known companies are good stock-market investment options, but in reality these two factors are largely unrelated . Anchoring and adjustment: This is another important heuristic according to which decisions made by humans are dependent on some key value/number.There is no process or logic behind determination of this value/number it could be any random number. For example, budgeting which involves use of current figures to determine future estimates. Many fund managers use current year figures and current year industry averages to determine future estimates. This bias is a product of our inherent conservatism which leads to our under reaction to new information. Institutional investors are more prone to this bias as compared to small investors. Probably because the managers of investment c ompanies actively use these techniques to draw conclusions.Small investors would hardly be aware so these techniques however those with an accounting background could be an exception . Loss aversion: It is also a key bias. It is based on the concept that humans find it very difficult to accept loss and the state of denial is such that we infact believe that holding onto it for longer periods of time would turnaround things some way or the other. This bias has some major consequences in financial decision-making. For instance, over the years it has been seen that many companies have kept running loss-making units and destroying shareholder wealth to the level at which it was irreparable.The reasons behind the strength of this bias as scholars put it is the shame and regret and feeling the blame for the loss incurred. Individual investors are more prone to this professional investors, a study revealed that individual investors sell those stocks that start to perform well quite soon an d hang on loss-making stocks for longer periods of time hoping that things might take a u-turn. This problem as professional traders put it is named get evenitis. Hindsight bias: It is based on the concept that humans are prone to that feeling â€Å"I knew it all the while† or precisely hindsight bias.To correct this bias is also very difficult because it’s natural for us to make differing conclusions regarding what happened in the past even though those decisions would have been correct according to the data and circumstances at hand then. For example, these days since the global economy is in recession even a layman is heard that this was inevitable. Individual investors are prone to this bias out of human nature, as for institutional investors they are less prone to this because they would be having greater access to information all the time .Over-confidence bias: Humans are naturally over-confident about their abilities normally. This further leads to over optimism i. e. we normally feel that we can be successful in most of our endeavors or do the right thing in most of the situations. However in reality that is not possible. Moreover the more information or data one gathers regarding a task, the more that person feels in greater control this is called Illusion of knowledge. Practically the biggest setback that one has to deal with results unfolds is that they are quite different than what was expected.Individual investors are much less prone to this bias as compared to institutional investors which suffer a lot more, because the over-confidence of a team of managers would prove more lethal financially. For example, 3Com which acquired US Robotics in 2000 made an IPO of its division that made the famous Palm pilots. Although the share prices went as high as $165 making 3Com the fourth largest technology firm then but announcement of a forthcoming product without the infrastructure yet in place saw its share prices dramatically fall to $1. 35 in 2001.This financial blunder was a result of a combined over-optimism of the then senior management. INVESTMENT BELIEFS: Characteristics of the Individual investor’s investment beliefs would be focused on limited aspects probably because they have limited knowledge of the market and they invest smaller amounts as compared to institutional investors. They would probably invest in companies that have good market reputation and which promise a good return within a short span of time. As for institutional investors their investment beliefs would be diverse since they are professionals.It would be important for them to take measures to avoid conflicts of interest. It would also be important for them to develop a clear view of capital markets in order to invest in companies that are expected to yield good returns . CONCLUSION: Behavioral finance has therefore highlighted that financial decision-making of both individual and institutional investors. The errors/mistakes made in yes ter-years both at the individual and organizational level if taken care of in future could result in making sound long-term decisions. WORKS CITED: Blanco. A.Behavioral Finance Possibilities and Limitations of Different Approaches. Wiesbaden, 2003 Fortune. Why CEOs Fail. February 10th 2009 Retrieved from :< http://money. cnn. com/magazines/fortune/>, 1999. Goldberg. J. Behavioral Finance. John Wiley, 2001. Montier. J. Behavioral Finance: Insights into Irrational Minds and Markets. J. Wiley. 2002. Owen. A. S. Behavioral Finance and the Decision to Invest in High Tech Stocks. School of Finance and Economics, University of Technology, 2002 Pompian. M. M. Behavioral Finance and Wealth Management: How to Build Optimal Portfolios That Account for Investor Biases.John Wiley and Sons, 2006. Redhead. K. Personal Finance and Investments: A Behavioral Finance Perspective. Routledge, 2008 Shefrin. H. Behavioral Finance. Edward Elgar Pub, 2001. Shleifer . A. Inefficient Markets: An Introduction to Behavioral Finance. Oxford University Press US, 2000. Stanyer. P, Dimson. E. The Economist Guide to Investment Strategy: How to Understand Markets, Risk, Rewards and Behaviour. Bloomberg Press, 2006. Taffler. J. R. (2001). Management Focus. Thaler. H. R. (1993). Advances in Behavioral Finance. Russell Sage Foundation

Love Is A Powerful Feeling Essay - 1353 Words

Love is a powerful feeling; it makes you do crazy thing. Many people spend years trying to find it, others give up thinking they’ll never find it. Love has been defined as an intensive feeling of a deep romantic or sexual attachment to someone. Of course, Love doesn t have to romantic and/or sexual. People who are ace, as in asexual, aromantic and agender, can still be in relationships that are satisfying for them without the needs of a romantic relationship. Familial love is also non-romantic-sexual. However, in this paper, we will be talking about romantic-sexual love, what it is, and why I believe it’s so important to understand and experience. Like I mentioned in the paragraph above love is usually defined as an intensive feeling of a deep romantic or sexual attachment to someone, however love is a bit more complicated than that. Love is special, it’s unique in it’s attitude and behavioral components, it’s a phenomenon that eludes easy definitio n (Our Sexuality, 2012). Love has always been a complicated subject; sometimes love is fickle, sometimes love isn’t love, but rather pure infatuation. Infatuation is often mistaken for love, however it is only a short lived but intense passion for someone. It’s possible that since many infatuations are mistaken love that many researches regarding the measurements of love would include individuals infatuated with each other. In one possible case, a man named Zick Rubin wished to measure love and liking. He set up 13 questionsShow MoreRelatedTheme Of Sonnet 1161025 Words   |  5 PagesLove is an emotion and feeling that will either fade away as time goes by or stay with a person for a lifetime. Love is not only between opposite sexes but rather between the thought of humankind. 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