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Test your drug discovery knowledge with TRC’s Christmas Quiz

 

Please join us in celebrating more than 100 years of incredible drug discovery advances and innovations with TRC’s Christmas quiz - authored by LGC’s Dr Joe Lackey. Find out how much you know about subjects ranging from trail-blazing scientists in biophysics to medchem theory, innovations in targeted oncology, structure-based drug design and fragment-based discovery. We hope you have as much fun answering these questions as we did compiling them!

 

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Question 1. What was the first synthetic drug?

A. Aspirin / acetylsalicylic acid

B. Chloral hydrate / Notec

C. Chlorpromazine / Thorazine

D. Paracetamol

 

Question 2. Which pharmaceutical company invented and first marketed the blockbuster drug Aspirin?

A. Bayer

B. Pfizer

C. AstraZeneca

D. Merck & Co

 

Question 3. What was the first targeted cancer therapy?

A. Tamoxifen

B. Herceptin

C. Gleevec

D. Dasatinib

 

Question 4: Which trailblazing scientist first published the structure of penicillin, as determined using the biophysical technique x-ray crystallography?

A. Linus Pauling

B. Edward M. Purcell

C. Dorothy Crowfoot Hodgkin

D. Felix Bloch

 

Question 5. Which of the following is often cited as the first example of the application of structure-based drug design leading to an approved drug?

A. Dorzolamide

B. Tamoxifen

C. Erlotinib

D. Imatinib

 

Question 6. The first highly successful HIV protease inhibitor was approved by the FDA in 1995. What was it called?

A. Saquinavir

B. Lamivudine

C. Raltegravir

D. Efavirenz

 

Question 7. Lipinski’s rule of 5 states that a drug should have a molecular mass of no more than…?

A. 1000da

B. 750da

C. 500da

D. 250da

 

Question 8. What was the first monoclonal antibody approved for cancer therapy by the US FDA?

A. Rituximab / Mabthera

B. Muromonab-CD3 / Orthoclone OKT3

C. Bevacizumab / Avastin

D. Atezolizumab / Tecentriq

 

Question 9. In Fragment Based Drug Discovery, small molecule fragment characteristics were laid out by Miles Congreve in a landmark 2003 study.  What is the name of the rule he coined?

A. Rule of two

B. Rule of three

C. Rule of four

D. Rule of five

 

Question 10. ISM001-055 was the first drug approved to enter phase I clinical trials that was wholly generated by AI. But what condition was it designed to treat?

A. Idiopathic Pulmonary Fibrosis

B. Diabetes

C. Thyroid Cancer

D. Parkinson’s Disease

 

 

 

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ANSWERS

 

Question 1. What was the first synthetic drug?

 

Answer: B. Chloral hydrate/Notec

 

Did you know…? In 1832, Justus von Liebig, a leading nineteenth century organic chemist prepared chloral hydrate by performing a chlorination reaction on ethanol - further demonstrating that, in alkaline solution, chloral hydrate is converted into chloroform and formic acid. This encouraged the German physician and pharmacologist Oscar Liebreich (1839–1908) to explore whether the same reaction might occur directly in the blood, which would mean that chloral hydrate might also be a useful anaesthetic, working in a similar way to chloroform. Further studies at the time showed that chloral hydrate was a relatively safe sedative. It entered the pharmacopeia in 1869 and still exists today in some countries as Noctec.

 

Question 2. Which pharmaceutical company invented and first marketed the blockbuster drug Aspirin?

 

Answer: A. Bayer

 

Did you know…? One hundred and twenty-five years ago, a German chemist working for the Bayer company named Felix Hoffman modified salicylic acid to create acetylsalicylic acid, which was subsequently named aspirin. Sold by Bayer from 1899, aspirin became a highly successful pharmaceutical product - although plant extracts rich in salicylates have a much longer history and were used for the treatment of fevers and other illnesses in ancient times. Plants, shrubs, and trees of the genus Spiraea contain salicin, a natural glycoside of salicyl alcohol, which after hydrolysis and oxidation gives salicylic acid.

 

Question 3. What was the first targeted cancer therapy?

 

Answer: A. Tamoxifen

 

Did you know…? The first targeted cancer therapy is widely regarded to have been tamoxifen, approved in 1972 in the UK, and 1977 in the USA. Tamoxifen binds to the oestrogen receptor, preventing binding of the hormone oestrogen - thereby modulating receptor activities, as well as reducing growth and proliferation of oestrogen receptor-driven malignancies.

 

Question 4: Which trailblazing scientist first published the structure of penicillin - as determined using the biophysical technique x-ray crystallography?

 

Answer: C. Dorothy Crowfoot Hodgkin

 

Did you know…? In her own words, “Captured for life by chemistry and by crystals,” Dorothy Hodgkin turned a childhood pastime into the ground-breaking use of X-ray crystallography – allowing us to “see” the molecules of penicillin, vitamin B12 and insulin. Her genius not only allowed researchers to better understand and manufacture life-saving substances, but also made crystallography an indispensable scientific tool. Hodgkin won the Nobel Prize for Chemistry for this and other work in 1964.

 

Question 5. Which of the following is often cited as the first example of the application of structure-based drug design leading to an approved drug?

 

Answer: A. Dorzolamide

 

Did you know…? Structure based drug design (SBDD) involves designing bespoke drugs based upon the three-dimensional structure of their biological drug targets, obtained from techniques such as X-ray crystallography and NMR spectroscopy.

 

The carbonic anhydrase inhibitor dorzolamide was approved by the FDA in 1995, and is used to treat high blood pressure inside the eye. One of the first SBDD successes, dorzolamide was achieved by researchers who had access to crystals of carbonic anhydrase, in complex with drug binding candidates such as MK-417 and its enantiomer. From this, they were able to hypothesise structural changes that would improve drug binding characteristics -  thereafter calculating quantum mechanics energetics using a 1980s computer to find evidence of how to stabilise the conformation that became dorzolamide.

 

Question 6. The first highly successful HIV protease inhibitor was approved by the FDA in 1995. What was it called?

 

Answer: A. Saquinavir

 

Did you know…? The human immunodeficiency virus (HIV) was first documented in San Francisco and New York City in 1981. Then, four years later, scientists declared HIV as the causative agent of acquired immunodeficiency syndrome (AIDS). 

 

By 1987, highly selective HIV protease inhibitors had been identified, and in June 1995, the FDA approved an open label study of saquinavir – an antiretroviral drug that targets HIV protease and prevents the virus from replicating. Six months later, saquinavir was approved for use in combination with other nucleoside analogue medications – ushering in the age of combination therapy, and a new era of highly effective anti-HIV therapies. Today, the FDA has approved 26 AIDS drugs, 10 of which are protease inhibitors.

 

Question 7.  Lipinski’s ‘rule of five’ states that a drug should have a molecular mass of no more than?

 

Answer: C. 500da

 

Did you know…? Formulated in 1997 by Christopher A. Lipinski, the ‘rule of five’ is also a  ‘rule of thumb’ to evaluate drug likeness, or determine if a compound with a certain biological activity has properties that would make it a likely orally active drug in humans. It is based on an observation that most orally administered drugs are relatively small and moderately lipophilic. The rule states that, in general, an orally active drug does not violate the following criteria any more than once:

 

-  No more than five hydrogen bond donors (the total number of nitrogen–hydrogen and oxygen–hydrogen bonds)

 

-  No more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms)

 

-  A mass of less than 500 Daltons

 

-  A calculated octanol-water partition coefficient (Clog P) of no more than five.

 

The reason for the rule’s name is that all of its numbers are multiples of five. However, as with many other rules of thumb, such as the rule of 3, there are many exceptions to it.

 

Question 8. What was the first monoclonal antibody approved for Cancer Therapy by the US FDA?

 

Answer: A. Rituximab / Mabthera

 

Did you know…? Rituximab became the first monoclonal antibody approved by the FDA for treatment of cancer, and specifically lymphoma malignancies, in 1997. Since then, several monoclonal antibodies have received FDA approval for the treatment of a variety of solid tumours and blood cancers - acting through a number of mechanisms, including immunotherapy and blockage of growth factor signaling.

 

Question 9. In Fragment Based Drug Discovery, small molecule fragment characteristics were laid out by Miles Congreve in a landmark 2003 study.  What is the name of the rule he coined?

 

Answer: B. Rule of three

 

Did you know…? Fragment Based Drug Discovery (FBDD) is nowadays a well-established and widely adopted approach that starts with the generation of libraries of small molecules called “fragments” - from which drug candidates are identified and further developed. When FBDD was first conceived, it was proposed that these fragments should, as a general rule, adhere to specific physical and chemical property guidelines (as laid out by Dr Miles Congreve and colleagues in a landmark 2003 study). Congreve proposed the so-called “rule of three”, which states that fragments should generally adhere to the following molecular properties:

 

-  a molecular weight smaller than 300da

 

-  lipophilicity as expressed by C Log P smaller than three

 

-  fewer than three hydrogen bond donors and acceptors

 

-  the number of rotatable bonds should be less than three

 

The rule of three has since been the subject of extensive challenge and remains a source of lively debate

 

Question 10. ISM001-055 was the first drug approved to enter phase 1 clinical trials that was wholly generated by AI. But what condition was it designed to treat?

 

Answer: A. Idiopathic Pulmonary Fibrosis

 

Did you know…? In February this year, Insilico Medicine achieved a major milestone in the history of AI for drug discovery when it announced a Phase I clinical trial of its first-in-class, anti-fibrotic drug candidate ISM001-055. The company’s achievement is notable because ISM001-055 is the world’s first drug developed from scratch, entirely using AI, to undergo a Phase I trial and be tested on a large number of humans. Insilico’s platform applied AI to biology for target discovery and to chemistry for drug design. Remarkably, the total time from the initiation of the target discovery programme to Phase I was less than 30 months. 

 

 

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