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Identification of osimertinib (AZD9291) as a lysine specific demethylase 1 inhibitor
Affiliation:1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China;2. Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China;3. Key Laboratory of Technology of Drug Preparation, Ministry of Education of China, Zhengzhou 450001, PR China;4. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, Jiangsu, PR China;1. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China;2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, Jiangsu, China;3. Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Zhengzhou University, Zhengzhou 450001, China;4. Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, Zhengzhou University, Zhengzhou 450001, China;5. Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China;1. Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China;2. School of Biology and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212018, China;1. Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India;2. Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India;3. College of Pharmacy, Department of Pharmacognosy, Prince Sattam bin Abdul Aziz University, Al-Kharj, Saudi Arabia;1. Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China;2. The School of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China
Abstract:Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In this study, osimertinib was characterized as a LSD1 inhibitor for the first time with an IC50 of 3.98 ± 0.3 μM and showed LSD1 inhibitory effect at cellular level. These findings provide new molecular skeleton for dual inhibitor for LSD1 and EGFR. Osimertinib could serve as a lead compound for further development for anti-NSCLC drug discovery with dual targeting.
Keywords:Osimertinib (AZD9291)  Lysine specific demethylase 1  Inhibitor  NSCLC
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