Overcoming the challenges of infrared photosensitizers in photodynamic therapy: the making of redaporfin

We offer a personal account of the discovery and development of a photosensitizer for photodynamic therapy (PDT) of cancer, from bench to bedside. We emphasize the more chemical aspects of drug discovery and drug development, namely the chemical landscape at the time of the discovery, the breakthrough in the field offered by stable bacteriochlorins, the challenges of synthesising a significant amount of the product with high purity for preclinical studies, the factors that relate molecular structure to pharmacology in PDT, the mechanistic interpretation of preclinical data and the management of unexpected results. Special attention is given to the implications of atropisomerism and immune responses in PDT.