HISTORY

Existed for almost as old as human history. it started with ___ and gradually evolved into a process that was strongly based on scientific evidence and involved multidisciplinary studies

Drug discovery

serendipitous discovery

provided a brief view of the transition from traditional drug discovery to modern drug discovery and particularly emphasized the protocol involved in drug development

Umashanka & Gurunathan

reviewed the impacts of molecular biology on drug discovery development

Drews

focused on the pivotal technologies in the drug discovery process.

Gershell and Atkins

presented challenges of drug discovery after the COVID 19 pandemic

Villoutreix

knew about using bitter plants with poison or psychotropic plants for self-medication

Paleolithic humans

human race settled from nomad life and grow their plants for food, setting off the agricultural evolution that brought civilization as well as plagues of infectious diseases

10,000 years ago

primary source of medicine for the treatment of diseases, which were mostly discovered by chance

plants

Some of the “drugs” discovered were without medicinal value such as

alcohol and tea

some other drugs discovered that are harmful and addictive

cannabis and opium

The functions of plants as medicines were transmitted ___ and the practices were greatly affected by ___

verbally or engraved on caves

cultures and religions

The practices of Egyptian medicine can be found in a few documents such as? which was produced in?

Ebers Papyrus

1536 BCE

Ebers Papyrus is one of the oldest medical documents that recorded some disease conditions and the use of ___ that originated from plants to produce ___

328 ingredients

876 prescriptions

At around ___, the Greeks transformed the superstitious beliefs in medicine by introducing ___, under the influence of Greek philosophers such as ___ and ___

500 BCE

empirical rational-based medicine

Empedocles

Pythagoras

Greek physician who is renowned as the ‘Father of Medicine’. He created the?

Hippocrates

Hippocratic Corpus

The Hippocratic Corpus included around ___ and influenced the ___

130 medicines

Galenic medicine

Greek physician ___ systematically documented ___ used as drugs in ___which laid the foundation of ___ medicine

Pedanius Disocorides

500 plants

De Materia Medica

homoeopathic

During the ___ (___ century), translation projects were implemented by the rulers and those collections of books from ___, and other countries were translated, studied, and modified into Arab

Golden period of Arab science

9th to 13th

Greek, Roman, Persian, Indian, Chinese, Syrian

___ were adopted and modified by Arabic physicians based on their studies and experience

Hippocratic and Galenic medicines

The practices and development of medicine blossomed with the rise in the civilization of Arabs. They set up the ___ in history and built a ___ that operated independently

first apothecary

hospital with an apothecary

Muslim scholar, produced a book named “___" which defined the role of a pharmacist. These developments planted the root of the pharmacy profession

Al-Biruni

Saydanah Fit-Tibb

most popular medicinal system in India

Ayurveda

Ayurveda is also known as ‘___’, and has been established since the ___

the science of life

2nd century BCE

Ayurveda is a sophisticated ancient medicine that developed a treatment based on ___

products, diet, lifestyle, and environment

recorded the categories, properties and pharmacology of over ___ in Ayurvedic medicine

Charak Samhita and Sushrut Samhita

700 plants

Ayurveda involves the use of ___ in treatment as well as the knowledge of ___ of those materials

plant and animal products, minerals and metals

collection, preparation, and storage

In ___ use of herbs and materials that originated from other natural resources has been the main practice in ___ since the ___ (AD 25 – 220)

China

Traditional Chinese Medicine (TCM)

Eastern Han Dynasty

Chinese medicine was developed from ___ to the establishment of systematic herbal medicines

trial and error

A few documents of TCM were produced and the most famous compilation was ‘___’ or “___”

Compendium of Materia Medica

Ben Cao Gang Mu

TCM comprises more than ___ which can be categorized based on tastes and four properties, as well as the site of action

11,000 documentary herbs

The herbal formulation in TCM and the herbs’ interaction were studied based on the herbs’ ___

taste, properties, site of actions, and seven relations theory

Ancient medicine records produced in Europe

Greece

• Hippocratic corpus

• De materia medica

Ancient medicine records produced in Middle East

Egypt

• Kahun Papyrus

• Ebers Papyrus

Arab

• Saydanah Fit-Tibb

Ancient medicine records produced in Asia

India

• Charak Samhita

• Sushrut Samhita

China

• Compendium of Materia Medica

among the oldest practising medicine in the world and both medicines are still popular in China and India today.

Chinese med and Ayurveda med

From ___, natural resources believed to have beneficial values continued to be discovered.

ancient times until the 17th century

___ was found to relieve migraine and help in digestion in 800 BCE

Coffee

___ was discovered in 1532 and was used to relieve pain and feelings of starvation

coca

Coca is one of the ingredients in ___, a drink which was first introduced in 1885. The drink was reformulated in 1907 and the coca leaves were ___ before being used in the formulation

Coca-Cola

decarbonised

discovered in 1639 was ___ which was used to treat malaria fever

cinchona bark

In 1681, ___ was found to have a therapeutic effect on iron deficiency illnesses

ferrous sulfate

In the ___, the practices of clinical trials and preventive medicine were started when ___ reported his study on the ___ with his established first controlled clinical study in 1753 which founded the concept of ___

18th century

James Lind

prevention of scurvy

scientific testing on drug efficacy

In 18th century: In ___, the first vaccine was born when an English physician ___ used ___ to immunize people for the prevention of ___which eventually led to the eradication of this diseases in ___

1796

Edward Jenner

cowpox

smallpox

1979

18th century: in 1979, ___ was founded by ___

homeopathic medicine

Samuel Hahnemann

In the ___, the advancement of chemistry allowed the ___ from herbal plants bringing drug discovery to ___

19th century

extraction and isolation of active substances

small molecule drug discovery

19th century: In the ___ important active substances such as ___ were first extracted and isolated from the plants

early 1800s

alkaloids, morphine, quinine, and atropine

19th century: ___ is still the most effective painkiller for severe pain today.

Morphine

19th century: Advances in synthetic chemistry led to the production of ___, the blockbuster drug derived from ___

Aspirin

salicylic acid

19th century: Aspirin was marketed as an ___ in 1899 and was effective in relieving pain and anti-inflammation

analgesic

19th century: In 1982, owing to the ___ effect of aspirin, it was repurposed for use in ___

antiplatelet

cardiovascular disease

19th century: Progress in ___ was also observed in the 19th century.

biomedicine

19th century: A new discipline known as ___ was founded by ___ in 1847, to understand the physiology of organisms and relate it to therapeutics

pharmacology

Rudolf Buchheim

19th century: ___ after the establishment of pharmacology discipline, German pathologist ___ proposed ___ which strengthened the knowledge in ___

11 years

Rudolf Virchow

cell theory

biology, cell pathology and medicine

19th century: ___ is a chemist who discovered the science of ___ and in 1878, he proposed the ___ which played an important role in the development of ___ and ___ in medicine

Loius Pasteur

isomers and stereochemistry

germ theory

vaccination

sterilization or aseptic technique

Another important achievement in the late 19th century was the introduction of ___ by ___ which boosted the development of ___ (Valent et al., 2016). This also created interest in the ___ or ___

receptor-ligand theory

Paul Ehrlich

chemotherapy

ligand-receptor approach

target-directed drug discovery

drug discovery research from the 18th century

1753: publication of first controlled clinical study

1796: first vaccine (smallpox vaccine) & founded homeopathic medicine

drug discovery research from the 19th century

early 1800s: extraction and isolation of active substances from plants

1847: establishment of pharmacology

1858: introduction of cell theory

1878: introduction of germ theory and aseptic technique

1899: first synthetic drug (aspirin)

1900: introduction of receptor-ligand theory

Drug discovery since the 20th century

Isolation of therapeutic substances from non-plant sources

Cell therapy

Computational drug discovery

Development of recombinant DNA

Molecular biology directed drug discovery

20th century isolation of therapeutic substances from non-plant sources: Drugs that did not originate from plants started to be produced.

Isolation of therapeutic substances from non-plant sources

In the early 20th century,

___ isolated from ___: treat ___

___ from ___: treat ___

heparin

dog’s livers

blood clots

insulin

dog’s pancreas

severe diabetes

20th century: Antibiotic drugs such as ___ were isolated from the ___ while ___ were isolated from ___

penicillin, ciclosporin, and tacrolimus

fungus

streptomycin and tetracyclines

soil bacteria

___ is the first antibiotic drug discovered by ___ in 1928

Penicillin

Alexander Fleming

successful elucidation of penicillin structure subsequently produced many other structure-related antibiotics such as ___

ampicillin

___ remains one of the most commonly used antibiotics today

Penicillin

___ was discovered to be able to diminish fever, however, it was also found to cause ___

acetanilide

hematotoxicity

The discovery of acetanilide led to the synthesis of ___ used as an ___ in the first few decades of the 20th century

phenacetin

antipyretic

The metabolites of Phenacetin were analysed and it was found to produce ___. On the other hand, one of its metabolites was found to be a reactive compound known as ___, which became a blockbuster antipyretic after its introduction in 1953

toxic anilide

acetaminophen or paracetamol

first direct blood transfusion between humans in surgery was conducted successfully signifying the start of ___

cell therapy

the first bone marrow transplantation to cure ___ was conducted and initiated studies in therapy using ___

aplastic anaemia

bone transplantation

the ___ were used to produce the first ___ and the potency of it in cell therapy has been studied intensively until now

murine embryos

stem cell

Before the 1950s, the discovery of drug compounds was through ___ of a large number of natural or synthetic compounds.

indiscriminate screening

Together with the advancement of ___ and the concept of drug actions, ___ started to be adopted in drug discovery research

organic synthesis

rational drug design

rational drug design was followed by the introduction of the ___

quantitative structure-activity relationship (QSAR)

the publication of the article “___” in Fortune magazine captivated high attention of researchers in ___

The Next Industrial Revolution: Designing Drugs by Computer at Merck

computational aided drug design (CADD)

___ was first introduced and large libraries of small molecules can be generated for high-throughput screening

combinatorial chemistry

A large number of compounds in the screening libraries were found failed to identify promising drugs, instead ___ is more practical when a small library focuses on certain scaffolds and adoption of ___ methods together in drug discovery

combinatorial library

hit-to-lead optimization

CADD had successfully brought a few drugs to approval which included ___ for hypertension (1981), ___ for glaucoma (1995), ___ for HIV (1995), ___ for HIV (1996), ___ for influenza virus (1999), and ___ for hypertension

captopril

dorzolamide

Saquinavir

ritonavir and indinavir

zanamivir

Aliskiren

Discoveries of ___ started in the 1950s and the first experiment was conducted in ___

restriction enzymes

1971

restriction enzymes set off the development of ___ and transformed the chemistry-based drug discovery industry. This enabled the production of the first peptide based drug, ___

recombinant DNA

Humulin or human insulin

not only peptide-based drugs but biological drugs also have been produced such as ___, which is a ___

trastuzumab (Herceptin)

monoclonal antibody

One of the biggest contributions to molecular biology and drug discovery research is the initiation of the ___ and took ___ to finish and eventually launched a ___

Human Genome Project (HGP)

15 years

post-genomic era

Along the way, HGP set off the application of ___, fostered the development of ___ and the advancement of multi disciplines such as computational and mathematics

“big data” science

omics technologies

The understanding of ___ has also been improved and steered the drug discovery research perspective to ___ which the drug is developed and evaluated not only from its structure but also from its action mechanisms as well as its effect on interactions within biological systems

biomedical sciences

systems biology

HGP also aided in identifying new potential targets for diseases which eventually drifted the ___ to ___

phenotypic drug discovery

target based drug discovery

Another breakthrough in molecular biology-directed drug discovery is the advancement of ___

gene therapy

Gene therapy has come a long way from the failure of its first clinical trial in ___ and finally attained success in the treatment of ___ in 2011. From 2011 to 2020, the number of approvals for gene therapy products reached ___

1988

haemophilia B

16

The functions of small molecules

RNA targeting molecules, protein-protein interaction inhibitors, antibody-drug conjugates compounds, PROTACs

small molecules are also developed as ___ to investigate biological systems

molecular probes

The drug discovery and development in the 19th century had started industrialised leading to an increase in drug trading and problems such as ___

false labels or unsafe medications.

To tackle the problems of unsafe medications, the ___ was approved in the United States in ___ and the ___ was founded which changed to the ___ in ___

Pure Food and Drug Act

1906

Bureau of Chemistry

Food and Drug Administration (FDA)

1930

unprecedented successful drug discovery in the 20th century has experienced two major drug disasters. the production of ___ using ___ as a solvent which caused the death of patients in the United States and led to the approval of the ___. Since then, the test for ___ has become compulsory before being marketed

elixir sulfanilamide

toxic diethylene glycol

Federal Food, Drug, and Cosmetic Act in 1938

drug toxicity and FDA approval

Another disaster happened in 1957 in countries including the ___ due to thalidomide

United Kingdom, Canada, Africa, Australia, Japan, and Europe

___ was marketed as a sedative to treat nausea and morning sickness during pregnancy however caused severe birth defects and affected approximately ___ children. banned in ___

Thalidomide

10,000

1961

___ rules and regulations have become the golden standard reference for drug regulation

FDA

FDA approved ___ which included ___ and ___ to ensure the public has some basic understanding of the medicine they use

direct-to-consumer advertisements

disease-awareness ads

product-claim ads

Highlights of drug discovery research since the 20th century

the research and development cost in drug discovery has increased dramatically but the rate of drug approval clinically remained stagnant

Current challenges and perspectives in drug discovery

Current challenges and perspectives in drug discovery

Complexity of the diseases

Knowledge gaps in new research fields and the use of cutting-edge technologies

Insufficiency of study in new human proteins as drug targets

Challenges in small molecule drug discovery

Research today faces the challenges of solving more complicated and difficult diseases such as

rare genetic diseases

multi-targets diseases

antimicrobial resistance

new and recurring viruses infections

diseases associated with ageing

more efforts are required to fill the knowledge gaps in the application of ___ to better translate drug actions and disease mechanisms in preclinical research as well as the clinical level

cutting-edge technologies