molecules of the month

X-165 is an autotaxin inhibitor clinical candidate for idiopathic pulmonary fibrosis discovered using a 3-cycle DEL screen of 225M compounds derived from amide couplings. An unusual spirocyclic amine building block was responsible for most of their non-phosphonate-containing high-enrichment hits. The initially resynthesized hits had single-digit nanomolar potencies in an enzymatic assay, and optimization for ADME properties while maintaining potency led to X-165.