Indoleamine 2,3-dioxygenase 1 (IDO1) has received increasing attention due to its immunosuppressive function in connection with various diseases, including cancer. A recent increase in the understanding of IDO1 has significantly contributed to the discovery of numerous novel inhibitors, but the latest clinical outcomes raised questions and have indicated a future direction of IDO1 inhibition for therapeutic approaches. Herein, we present a comprehensive review of IDO1, discussing the latest advances in understanding the IDO1 structure and mechanism, an overview of recent IDO1 inhibitor discoveries and potential therapeutic applications to provide helpful information for medicinal chemists investigating IDO1 inhibitors.

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Cdc2-like kinases (CLKs; CLK1–4) are associated with various neurodegenerative disorders, metabolic regulation, and viral infection and have been recognized as potential drug targets. Human CLK2 has received increasing attention as a regulator that phosphorylates serine- and arginine-rich (SR) proteins and subsequently modulates the alternative splicing of precursor mRNA (pre-mRNA), which is an attractive target for degenerative disease and cancer. Numerous CLK2 inhibitors have been identified, with several molecules currently in clinical development. The first CLK2 inhibitor Lorecivivint (compound 1) has recently entered phase 3 clinical trials. However, highly selective CLK2 inhibitors are rarely reported. This Perspective summarizes the biological roles and therapeutic potential of CLK2 along with progress on the development of CLK2 inhibitors and discusses the achievements and future prospects of CLK2 inhibitors for therapeutic applications.

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