1) Around 24% of drugs currently on the market were discovered through serendipitous events, with central nervous system drugs benefiting the most.
2) Some notable examples of serendipitous drug discoveries include penicillin discovered by Alexander Fleming, the anticoagulant warfarin discovered from cattle deaths, and cisplatin discovered by Rosenberg while studying E. coli bacteria.
3) Serendipity continues to play an important role in drug discovery, though some factors like rational drug design and shorter clinical observation times may be reducing its impact.
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
clinical and preclinical approaches to drug discovery.Here we mainly deals with preclinical approaches, ie. Pharmacological approach and toxicological approach
Target Validation
Introduction,Drug discovery, Target identification and validation, Target validation and techniques
By
Ms. B. Mary Vishali
Department of Pharmacology
PHARMACOHORE MAPPING AND VIRTUAL SCRRENING FOR RESEARCH DEPARTMENTShikha Popali
THE PHARMACOPHORE MAPPING AND VIRTUAL SCRRENING , THESE PRESENTATION INCLUDES THE DEATIL ACCOUNT ON PHARMACOPHORE, MAPPING, ITS IDENTIFIATION FEATURES, ITS CONFORMATIONAL SEARCH, INSILICO DRUG DESIGN, VIRTUAL SCREENING, PHARMACOPHORE BASED SCREENING
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
Drug discovery and development is and always has been the most exciting part of clinical pharmacology. It is my attempt to compile the basic concepts from various books, articles and online journals. Feel free to comment.
Target Validation
Introduction,Drug discovery, Target identification and validation, Target validation and techniques
By
Ms. B. Mary Vishali
Department of Pharmacology
PHARMACOHORE MAPPING AND VIRTUAL SCRRENING FOR RESEARCH DEPARTMENTShikha Popali
THE PHARMACOPHORE MAPPING AND VIRTUAL SCRRENING , THESE PRESENTATION INCLUDES THE DEATIL ACCOUNT ON PHARMACOPHORE, MAPPING, ITS IDENTIFIATION FEATURES, ITS CONFORMATIONAL SEARCH, INSILICO DRUG DESIGN, VIRTUAL SCREENING, PHARMACOPHORE BASED SCREENING
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
Drug discovery and development is and always has been the most exciting part of clinical pharmacology. It is my attempt to compile the basic concepts from various books, articles and online journals. Feel free to comment.
We are capable to formulate impressive range of bulk drugs. We provides these drugs using high quality ingredients to ensure pureness and long shelf life.
Drug design is the inventive process of finding new medications based on the knowledge of the biological target.
In the most basic sense, drug design involves design of small molecules that are complementary in shape and charge to the bio-molecular target to which they interact and therefore will bind to it.
Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is often referred to as computer-aided drug design.
Types;-
Random screening
Trial and error method
Ethnopharmacology approach
Serendipity method
Classical pharmacology
Chemical structure based drug discovery
Dispelling the Myths About Pharmaceutical R &DBilcareltd
Innovative research is done mainly by taxpayer funded research – government and universities funded by the NIH usually in universities and government labs and now in smaller biotech companies and then they license those to big drug companies.
Innovative research is done mainly by taxpayer funded research – government and universities funded by the NIH usually in universities and government labs and now in smaller biotech companies and then they license those to big drug companies.
0x01 - Newton's Third Law: Static vs. Dynamic AbusersOWASP Beja
f you offer a service on the web, odds are that someone will abuse it. Be it an API, a SaaS, a PaaS, or even a static website, someone somewhere will try to figure out a way to use it to their own needs. In this talk we'll compare measures that are effective against static attackers and how to battle a dynamic attacker who adapts to your counter-measures.
About the Speaker
===============
Diogo Sousa, Engineering Manager @ Canonical
An opinionated individual with an interest in cryptography and its intersection with secure software development.
This presentation by Morris Kleiner (University of Minnesota), was made during the discussion “Competition and Regulation in Professions and Occupations” held at the Working Party No. 2 on Competition and Regulation on 10 June 2024. More papers and presentations on the topic can be found out at oe.cd/crps.
This presentation was uploaded with the author’s consent.
Acorn Recovery: Restore IT infra within minutesIP ServerOne
Introducing Acorn Recovery as a Service, a simple, fast, and secure managed disaster recovery (DRaaS) by IP ServerOne. A DR solution that helps restore your IT infra within minutes.
Have you ever wondered how search works while visiting an e-commerce site, internal website, or searching through other types of online resources? Look no further than this informative session on the ways that taxonomies help end-users navigate the internet! Hear from taxonomists and other information professionals who have first-hand experience creating and working with taxonomies that aid in navigation, search, and discovery across a range of disciplines.
This presentation, created by Syed Faiz ul Hassan, explores the profound influence of media on public perception and behavior. It delves into the evolution of media from oral traditions to modern digital and social media platforms. Key topics include the role of media in information propagation, socialization, crisis awareness, globalization, and education. The presentation also examines media influence through agenda setting, propaganda, and manipulative techniques used by advertisers and marketers. Furthermore, it highlights the impact of surveillance enabled by media technologies on personal behavior and preferences. Through this comprehensive overview, the presentation aims to shed light on how media shapes collective consciousness and public opinion.
Sharpen existing tools or get a new toolbox? Contemporary cluster initiatives...Orkestra
UIIN Conference, Madrid, 27-29 May 2024
James Wilson, Orkestra and Deusto Business School
Emily Wise, Lund University
Madeline Smith, The Glasgow School of Art
2. SERENDIPITOUS DRUG DISCOVERY IN THE FIELD OF PHARMACY
Y. Srikala*, Jyothirmayee, S. Sharadha, V. Uma Maheshwara Rao
C.M.R College of Pharmacy, Kandlakoya (v), Medchal, Hyderabad – 501 401
Serendipity is not merely stumbling on things unsought for, it is the ability to see significances and find
values in the things stumbled upon. Serendipity means an aptitude for making desirable discoveries by
accident. It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity.
Of these drugs, 31 (2.2%) were discovered in the laboratory and 53 (3.7%) were discovered in a clinical
setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the
drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be
directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of
anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for
all drugs. Recently a new concept of Known Drug Space (KDS) has been developed to help drug designers
to navigate chemical space based on the analysis of drugs in clinical use. It is known that 10% of KDS are
unaltered natural products and 29% are their derivatives (semi-synthetics). The therapeutic field that has
benefited the most from serendipity is central nervous system active drugs reflecting the difficulty in
designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the
diseases of the mind.
In general, 24% of all pharmaceuticals currently on the market were affected in a positive way during their
development by this phenomenon with CNS active drugs being the most prominent. This leads to the
conclusion that drug discovery is based on good science and where intuition, critical thinking, sagacity and
open-mindedness play crucial roles.
3. INTRODUCTION
Serendipity is not merely stumbling on things unsought for, it is the ability to see significances and find values in the things
stumbled upon. Serendipity means an aptitude for making desirable discoveries by accident.
Nearly all the great discoveries in chemotherapy have been made as a result of a false hypothesis or due to a so-called chance
observation.
If the frontiers of knowledge is wide open, causes of phenomena mostly hide in the dark, where many scientists deem research
most challenging and exhilarating, chance and serendipity play bigger roles.
We explore the characteristics of a prepared mind in three cases. In the cases of scientists getting their ideas in dreams, we
examine the cognitive psychology of thinking and problem solving. The second case we take is one of the most famous
serendipitous drug discoveries, that of penicillin. Here we examine how the ability and inability to “connect the dots”
facilitated and limited Fleming’s contribution to the development of the antibiotic medicine. Many people would consider our
third case, drug screening, to be the antithesis of serendipity. Sure, instead of running into something unintentionally,
screening set out with the intention to find something
4. STATISTICS:
It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%)
were discovered in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the
pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in
total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this
elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is
somewhat larger than for all drugs
The distribution of the serendipity types (laboratory-based and clinical) and their chemical derivatives in clinical use (100% =
1437).
5. SERENDIPITOUS DRUG ACTS ON CARDIOVASCULAR SYSTEM:
During the 1920's, cattle began to mysteriously die from internal hemorrhage. The cause was attributed
generally to spoiled sweet clover, but when the Great Depression hit and ranchers could ill afford to lose a single
cow, one frustrated farmer, Ed Carlson, packed up his dead cow along with a milk can filled with blood that
refused to clot and drove to the Wisconsin Alumni Research Foundation (WARF) looking for answers. There
researcher Karl Link was able to isolate the naturally occurring chemical compound coumarin, which, when
oxidized in damp hay, is the culprit anticoagulant. In 1945, Link came up with the idea to use the compound as a
rodenticide, as it is still used today. Scientists continued to study and test coumarin.
In 1955, it was given to President Dwight Eisenhower after a myocardial infarction and today - from cattle-killer,
to rat-killer, to human life-saver -Warfarin is the most widely used anticoagulant in the world.
6. Figure 1. The systematization of serendipity.
Schlueter P J , and Peterson R T Circulation 2009;120:255-
263
7. SERENDIPITOUS ANTIBIOTIC DRUG:
Alexander Fleming didn't clean up his workstation before going on vacation one day in 1928. When he came
back, Fleming noticed that there was a strange fungus on some of his cultures. Even stranger was that bacteria
didn't seem to thrive near those cultures.
Penicillin became the first and is still one of the most widely used antibiotics.
8. In 1928, Scottish Scientist Sir Alexander Fleming was studying Staphylococcus – the bacteria that causes food
poisoning.
He turned up at work one day and discovered
a blue-green mould that seemed to be inhibiting growth of the bacteria. He grew a pure culture of the mould and
discovered
that it was a Penicillium mould.
9. SERENDIPITOUS ANTI DIABETIC DRUG:
Often several serendipitous discoveries contribute to the establishment of a major therapy.
Take for example insulin for diabetes. Chance observation of flies attracted to the sugar-rich urine of
experimental dogs with pancreas removed led to the discovery that the pancreas is causally related to
diabetes.
Since that discovery in 1889, many scientists tried to extract the pancreas’ secretion and use it as a
remedy for diabetes. Some almost made it; others failed, but not necessarily because they were more
ignorant.
When Frederick Banting, Charles Best, and John Macleod succeeded to extract insulin and demonstrate
its therapeutic efficacy in 1921, they designed their crucial experiment on a wrong conception
10.
11. SERENDIPITOUS ANTICANCER DRUG:
Nearly all the great discoveries in chemotherapy have been made as a result of a false hypothesis or due
to a so-called chance observation.
Chemotherapy involves the use of low-molecular-weight drugs to selectively destroy a tumor or at least
limit its growth.
Nitrogen mustards were the first agents to be used clinically; their use resulted from the accidental
discovery that the mustard gas used in world war II had antileukemic properties. Since then, important
advances have been made in the development of new anticancer drugs. For example, cisplatin, which was
also discovered serendipitously, provided a major advance in the treatment of testicular and ovarian
carcinomas.
12. The discovery of cis-platin was serendipitous. In 1965, Rosenberg was looking into the effects of an electric field on the
growth of Escherichia coli bacteria. He noticed that bacteria ceased to divide when placed in an electric field but what
Rosenberg also observed was a 300-fold increase in the size of the bacteria.
He attributed this to the fact that somehow the platinum-conducting plates were inducing cell growth but inhibiting cell
division. It was later deduced that the platinum species responsible for this was cis-platin.
Rosenberg hypothesized that if cis-platin could inhibit bacterial cell division it could also stop tumor cell growth. This
conjecture has proven correct and has led to the introduction of cis-platin in cancer therapy. Indeed, in 1978, six years after
clinical trials conducted by the NCI and Bristol-Myers-Squibb, the U.S. Food and Drug Administration (FDA) approved cis-platin
under the name of Platinol for treating patients with metastatic testicular or ovarian cancer in combination with other
drugs but also for treating bladder cancer.
13. Cisplatin is a chemotherapy drug commonly prescribed to lung cancer patients. Because it is administered systemically, the
entire body gets a hefty dose of the toxic substance with side effects that are often quite debilitating. To better target the drug
toward lung CA, researchers at the University of Strachlyde, Glasgow and TRANSAVE (Monmouth Junction, NJ) have
independently developed inhalation microcapsules that can contain cisplatin.
14. SERENDIPITOUS ANTIRHEUMATIC DRUG:
In 1996 we found by serendipity that 2 patients with rheumatoid arthritis (RA) who were taking clarithromycin (CM) to
eradicate Helicobacter pylori experienced a regression of their RA symptoms.
15. SERENDIPITOUS DRUG USED IN MYOCARDIAL INFARCTION:
A serendipitous discovery by William Smith Tillett in 1933, followed by many years of work with his student Sol Sherry, laid
a sound foundation for the use of streptokinase as a thrombolytic agent in the treatment of acute myocardial infarction.
The drug found initial clinical application in combating fibrinous pleural exudates, hemothorax, and tuberculous meningitis.
In 1958, Sherry and others started using streptokinase in patients with acute myocardial infarction and changed the focus of
treatment from palliation to “cure.”
16.
17. CURRENT STATUS OF SERENDIPITY
Several putative “anti-serendipity” factors that may interfere with current drug development have been identified.
These include 1) movement toward rational drug design based on translational research, 2) reduction in the amount of
time that clinicians have to observe patients, and 3) reliance on the double-blind placebo control design to
demonstrate efficacy..
The trend toward rational drug design is clear .However, its relationship to serendipity is opaque. Rational drug design
guided by translational research refers to the development of drugs deliberately designed to alter processes that have
been implicated in mental pathology by basic research
Another putative “anti-serendipity” factor is a constriction in the amount of time that clinical researchers have to
observe drug effects. Interestingly, this has been linked to the closing of long-term care mental hospitals (i.e.,
deinstitutionalization)
Another putative “anti-serendipity” factor is the use of the double blind placebo control design . The principal
objection to this design is that the design does not allow for analysis of individual differences in drug response.
The therapeutic field that has benefited the most from serendipity is central nervous system active drugs reflecting the
difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of
the diseases of the mind.
18. CONCLUSION:
In general, 24% of all pharmaceuticals currently on the market were affected in a positive way during their
development by this phenomenon with CNS active drugs being the most prominent. This leads to the conclusion that
drug discovery is based on good science and where intuition, critical thinking, sagacity and open-mindedness play
crucial roles.
Editor's Notes
Figure 1. The systematization of serendipity. Historically, cardiovascular drugs have been discovered through the serendipitous confluence of small molecules, organisms, and astute observations, as occurred in the discovery of dicoumarol (A). Some modern drug discovery efforts are systematically bringing together the same elements in the form of small-molecule libraries, screenable model organisms, and automated phenotyping systems in an effort to discover novel therapies for cardiovascular diseases (B).