Old tricks and new trends to address tumors: a medicinal chemist’s perspective

Major efforts in the past decades have provided novel small molecule drugs and biologicals and innovative mechanisms against tumors, but the quest for safer, bioavailable and more effective active principles is still ongoing. This contribution focuses on innovative approaches to fulfill therapeutic goals in oncology; namely, the inhibition of the stabilizing interaction between the RNA-binding protein HuR and mRNAs of multiple oncogenes, and the unleashing of a strong immune reaction against cancer cells by antagonizing the PD-1 – PD-L1 interaction on the surface of cancer cells. “Classical” drug-like, bioavailable small molecules were either rationally designed from a naturally occurring template (tanshinones converted to aza-tanshinones – HuR), or from a synthetic peptidomimetic inhibitor (biphenyloxy aryls converted to disubstituted triazines – PD-L1); after their synthesis and activity profiling, early leads were identified to be further structurally optimized in the near future.