New Quinoline Kinase Inhibitors With Good Selectivity for NAK Kinases and Anti‐Tumor Activity Against Ewing Sarcoma
In the past few years, several novel anticancer agents targeting protein kinases have been discovered expanding the available therapeutic arsenal. However, few new therapeutic approaches have been developed for the treatment of childhood cancer. To this end, we have been making efforts to contribute to this important field. Herein, we identified a series of new 4,6-disubstituted quinoline derivatives from our in-house quinoline chemical library that showed promising anti-proliferative activity against Ewing Sarcoma (ES). This interesting observation engaged us to further investigate these derivatives since this type of cancer is among the most common bone cancers in children. Evaluation of the quinoline derivatives against a panel of kinases demonstrated generally narrow selectivity profiles of this compound class. Interestingly, the main kinases that were inhibited belonged to the NAK family of kinases, in particular, the family member cyclin G-associated kinase (GAK) which was inhibited at nanomolar range in enzyme kinetic assays.
Authors
- André Luiz da Silva Santiago
- Mário Henrique Bengtson (ORCID: https://orcid.org/0000-0002-7474-1990)
- Katlin B. Massirer (ORCID: https://orcid.org/0000-0001-6390-2560)
- Stefan Laufer (ORCID: https://orcid.org/0000-0001-6952-1486)
- Henrique Barros de Lima (ORCID: https://orcid.org/0000-0002-8973-4902)
- Martha Cestari Silva Martins
- Lewis Elson (ORCID: https://orcid.org/0009-0004-6142-3653)
- Saulo Fernandes de Andrade (ORCID: https://orcid.org/0000-0003-2873-7939)
- Thaís Helena Maciel Fernandes (ORCID: https://orcid.org/0000-0001-5910-0792)
- Knapp Stefan
- Marcela Silva Lopes
- Rafael Roesler
- Caroline de Bem Gentz
- Lucas Rodrigo de Souza
- Geórgia Silva Pinto
- Lauro José Gregianin
- Isadora Serraglio Fortes
Institutions
- Goethe University Frankfurt (DE)
- Universidade Federal do Rio Grande do Sul (BR)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Hospital de Clínicas de Porto Alegre (BR)
- National Institute of Science and Technology (ID)
- University of Tübingen (DE)
Publication Details
- Journal
- Archiv der Pharmazie
- Published
- 2026-01-01
- DOI
- https://doi.org/10.1002/ardp.70184
- Primary Topic
- Melanoma and MAPK Pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bristol-Myers Squibb
- Pfizer
- Bayer
- McGill University
- Genome Canada
- Ontario Genomics
- European Federation of Pharmaceutical Industries and Associations
- Ontario Genomics Institute
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
- Genentech