To study ASK1 modulation’s implication on neurodegenerative diseases, Xin et al., discussed the design and synthesis of ASK1 inhibitors based on a previous work that identified a macrocyclic compound (cell IC50 = 95 nM) obtained from the lead compound (IC50 = 607 nM, cell IC50 > 20 μM) (Figure 12). The gene discussed is MAP3K5; the disease is neurodegenerative disease.