👶 You are wrong if you think that the thalidomide tragedy put an end to this molecule. Scientifically - with all due respect to harmed individuals - this molecule proved to be incredibly innovative, unlocking a completely new mechanism of action of "therapeutic glues".
❓ What is thalidomide? Why is one enantiomer safe and the other is not?
In this video, we uncover the history, chemistry, biology and pharmacology of thalidomide and related molecules like lenalidomide.

If you are a science enthusiast or interested in pharmaceuticals in general, this video is for you!

Disclaimer - This channel does not provide medical advice!
No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on Youtube.

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Note: A page abbreviates cereblon incorrectly as CBRN :)

00:00 Thalidomide - Horror Drug with Massive Profits?
01:35 Origins of thalidomide and Chemie Grünenthal
02:51 Initial findings of thalidomide side effects
03:45 Targeted protein degradation and molecular glues
06:19 Why did they not notice thalidomide side effects?
07:21 Chemistry and synthesis of thalidomide
08:47 Aftermath of thalidomide: Contergan trial
09:40 Thalidomide in the US: Narrowly avoiding a disaster
11:07 Learnings from the tragedy
11:55 Thalidomide benefit in leprosy and multiple myeloma
14:06 Lenalidomide, thalidomide's younger big brother - and lawsuits
16:51 More next-generation cereblon modulators (iberdomide)
17:56 Covalent modification of cereblon
18:40 THANK YOU!

Key references:
- Frances Oldham Kelsey. FDA medical reviewer leaves her mark on history | FDA Consum 2001, 35, 24
- The Thalidomide Syndrome | Scientific American 1962, 207, 29
- THALIDOMIDE AND CONGENITAL ABNORMALITIES | Lancet 1962, 279, 45
- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement | Int J Mol Sci 2020, 21, 6429
- Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment| Acta Pharmaceutica Sinica B 2022, 12, 3548
- Exploiting ubiquitin ligase cereblon as a target for small-molecule compounds in medicine and chemical biology | Cell Chem Biol 2021, 28, 987
- Crbn I391V is sufficient to confer in vivo sensitivity to thalidomide and its derivatives in mice | Blood 2018, 132, 1535
- Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs | PNAS 2015, E1471
- Lawsuit Blames Thalidomide for More Birth Defects | Scientific American 2011
- Antitumor Activity of Thalidomide in Refractory Multiple Myeloma | NEJM 1999, 341, 1565
- Immunomodulatory Drugs for the Treatment of B Cell Malignancies | Int. J. Mol. Sci. 2021, 22(16), 8572
- NPR.org “How A Drugmaker Gamed The System To Keep Generic Competition Away” (2018)
- A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos | J Med Chem 2018, 61, 535
- Cereblon covalent modulation through structure-based design of histidine targeting chemical probes | RSC Chem. Biol. 2022, 3, 1105

Some recommended books on organic synthesis:
- Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
- Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
- Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
- Nicolaou; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
- Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
- Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)