This lecture will summarize a personal perspective of key learnings from projects the author was involved in over the last 20 years, e.g. the discovery of macitentan, the most successful molecule to date from this personal collection, marketed by J&J for the treatment of pulmonary arterial hypertension (PAH) [1] or the discovery of ACT-462206, a dual orexin receptor antagonist for the treatment of insomnia with the shortest story from the screening hit to the drug [2] or the identification of ACT-541468, another dual orexin receptor antagonist in phase 3 clinical trials by Idorsia for the treatment of insomnia disorders [3] (“Good things come to those who wait”), and finally the selection ofACT-451840, an antimalarial drug with a novel mechanism of action, representing the most collaborative project in the authors experience resulting in a compound in phase 2 clinical development [4].

In addition, there will be a brief discussion on the importance of the screening compound collection, as a key asset for drug discovery, and the measures Idorsia implemented to obtain optimal hits from high-throughput screening (HTS) campaigns [5]. Drug discovery is a multi-disciplinary business with unlimited exciting challenges asking for excessive optimism when tackling them in a playful manner.

[1] M.H. Bolli, C. Boss, C. Binkert, et al; J. Med. Chem, 2012, 55, 7849-7864.
[2] C. Boss, C. Brisbare-Roch, M.A. Steiner, et al; ChemMedChem, 2014, 9, 2486-2496.
[3] A. Treiber, R. de Kanter, C. Roch, J. Gatfield, C. Boss, et al; J. Pharmacol. Exp. Ther., 2017, 364, 489-503.
[4] C. Boss, H. Aissaoui, N. Amaral, et al; ChemMedChem,2016, 11, 1995-2014.
[5] C. Boss, J. Hazemann, T. Kimmerlin, M. v. Korff et al; Chimia, 2017,71,667-677.