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Peer-Reviewed Publication
J Med Chem2024;67(23):20879-20910.December 12, 2024Journal Article

Discovery of UCB9386: A Potent, Selective, and Brain-Penetrant Nuak1 Inhibitor Suitable for In Vivo Pharmacological Studies.

Karine G Poullennec1, Eric Jnoff1, Jan Abendroth2, Naresh Bhuma3, Mark Calmiano4, Laurent Calmus5, Alvaro Cardenas1, Jean-Philippe Courade6, Claude Delatour1, Adrian Hall1, Teresa de Haro1, Silvia L Delker7, Thierry Demaude1, Nilesh Gaikwad8, Dnyaneshwar Ghavate8, Atul R Gholap8, Magdalena Kierkowicz9, Régis Le Mestre10, Nathalie Van Hijfte11, Simon Verheijden12, Katerina Vernerova9, Veerle De Wever1, Nivrutti Waghmode13
1Chemin du Foriest, UCB, 1420 Braine l'Alleud, Belgium.
2UCB Seattle, Bainbridge Island, Washington 98110, United States.
3Illumina Centre, 19 Granta Park, Great Abingdon CB21 6DF, United Kingdom.
4BenevolentAI, London W1T 5HD, United Kingdom.
5NovAliX, 240 Parc d'Affaires des Portes, 27100 Val-de-Reuil, France.
6Discoveric Bio α group, Bahnhofstrasse 1, CH-8808 Pfäffikon (SZ), Switzerland.
7UCB Boston, Cambridge, Massachusetts 01240, United States.
8Sai Life Sciences Ltd, IKP Knowledge Park, Genome Valley, Turkapally, Hyderabad 500078, India.
9UCB, Slough SL1 3WE, United Kingdom.
10Minoryx Therapeutics, Avenue Jean Mermoz 32, 6041 Charleroi, Belgium.
11NovAliX SAS, 16 rue d'Ankara, 67000 Strasbourg, France.
12Janssen Research and Development, Antwerpseweg 15, 2340 Beerse, Belgium.
13Squadron Life Sciences Pvt Ltd, Bhosari, Pune 411039, India.
PubMed DOI

Abstract

Nuak1 (NUAK family SnF1-like kinase-1) is a serine-threonine kinase and a member of the AMPK family. Interest in Nuak1 has increased over the years due to the role it plays in several biological processes, from tumor cell invasion and proliferation to Tau stabilization. Nuak1 is expressed in many cancer cell lines and many reports describe this target as an oncogene, the inhibition of which is hyp…

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