AZD-4205 | compound 21 [PMID: 32297743] | example 32 [US9714236B2] [1
] | JAK1-IN-3
AZD4205 is a selective, orally bioavailable, ATP-competitive inhibitor of Janus kinase 1 (JAK1) that was developed by Dizal Pharmaceutical Company [2
]. It has been shown to enhance antitumour activity in combination with osimertinib
(an approved EGFR inhibitor) in a preclinical non-small cell lung cancer xenograft model. A higher drug concentration within the gastrointestinal tract relative to plasma in preclinical models suggests potential to treat inflammatory bowel disease. Persistently activated STAT3 has been shown to be oncogenic, and drives expression of cellular proteins which contribute to central processes in cancer progression (survival, proliferation, invasion, angiogenesis). JAK1 is the key Janus kinase responsible for cytokine-mediated STAT3 activation.