Indoleamine 2,3-dioxygenase 1 (IDO1) is a valuable target in therapeutics since it is highly expressed in many tumors and plays an active role in tumor immune evasion. Balog and colleagues outline linrodostat mesylate and its potent, selective inhibition of IDO1. Linrodostat suppressed kynurenine production without any activity against similar enzymes such as tryptophan 2,3-dioxygenase (TDO2) or indoleamine 2,3-dioxygenase 2 (IDO2). Linrodostat showed single-digit nanomolar potency in vitro and in vivo. Taken together, the authors offer strong support for the ongoing clinical development of linrodostat in immunotherapy.

Previous research revealed that antagonizing cyclin-dependent kinase 1 or 2 (CDK1 or CDK2) leads to missegregation and apoptosis in daughter cells in a mechanism termed anaphase catastrophe. To generate anaphase catastrophe using a clinical candidate, Kawakami and colleagues utilized the CDK2/9 inhibitor CYC065. They confirmed anaphase catastrophe in lung cancer murine syngeneic and PDX models. The anti-neoplastic effects were robust to KRAS expression....

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