Rare genetic variability in human drug target genes modulates drug response and can guide precision medicine
Yitian Zhou, Gabriel Herras Arribas, Ainoleena Turku, Tuuli Jürgenson, Souren Mkrtchian, Kristi Krebs, Yì Wáng, Barbora Svobodová, Lili A. Milani, Gunnar Schulte, Jan Korábečný, Stefano Gastaldello, Volker Martin Lauschke · Science Advances · 2021
variant confers resistance to tacrine and rivastigmine, which can be overcome by the use of derivatives based on squaric acid scaffolds or tryptophan conjugation. These findings underscore the importance of genetic drug target variability and demonstrate that integration of genomic data and structural information can inform personalized drug selection and genetically guided drug development to overcome resistance.