This molecule might look like any other “flat drug” – but there is a hidden mystery behind its synthesis! Aside from the fact that it has shown promise in treating asthma due to its novel mechanism, one could say it's breathtaking (actually, it's pretty breathtaking, but I thought no one would understand that).
Watch this video to learn about organic synthesis, drug development, and much more!

00:00 A breathtaking synthesis
00:23 Structure of our target molecule
01:37 Introduction to PI3K enzymes and inhibitor drugs
03:41 Levels of sophistication in chemistry
05:09 AZD8154 retrosynthesis and overview
05:57 Advanced summary #1
07:26 What was the problem?
08:19 Advanced summary #2
11:10 How legitimate is the solution?
12:03 FDA position on PI3K inhibitors and conclusion

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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 professional with any questions you may have regarding a health problem or treatment and before undertaking a new health care regimen, and never disregard seek professional medical advice or never delay seeking it because of information on Youtube. .

Key references:
– Discovery of AZD8154, a dual PI3Kγδ inhibitor for the treatment of asthma J. Med. Chemical. 2021, 64, 8053
– Class I phosphoinositide 3-kinase isoforms PIK3CA/p110α and PIK3CB/p110β in endometrial cancer Int. J. Mol. Sci. 2018, 19, 3931
– The pathogenic role of the PI3K/AKT pathway in cancer onset and drug resistance: an updated review Cancers 2021, 13, 3949
– Discovery of phosphoinositide 3-kinase (PI3K)-γ inhibitors that are highly orally selective and bioavailable to isoforms J. Med. Chemical. 2018, 61, 5435
– A Diels-Aulne intramolecular approach to the isoindolinone core of AZD8154 doi.org/10.1021/acs.oprd.3c00507
– Selection and development of the manufacturing route of the EP1 antagonist GSK269984B Org. Process Res. Dev. 2010, 14, 820
– Characterization of pharmacokinetics, safety and tolerability in a first-in-human study for AZD8154, a novel inhaled dual selective PI3Kγδ inhibitor targeting inflammatory airway disease Br J Clin Pharmacol. 2022, 88, 260
– Copanlisib for the treatment of B-cell malignancies: development of a PI3K inhibitor with considerable differences compared to idelalisib Drug Des Devel Ther 2018, 12, 2577

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