Tumor hypoxia is a well-validated concept, but is yet to be successfully exploited in the clinic
Tumor hypoxia is known to promote the development of an aggressive phenotype, resistant to chemo, immuno-, and radiotherapy, and is strongly associated with poor clinical outcome. Given its central role in tumor resistance, hypoxia as an exploitable target became an important research area in oncology and the concept of prodrugs, compounds activated by enzymatic reduction in hypoxic tissue, are an attractive solution.
Although to date no Hypoxia-Activated Prodrugs (HAPs) have been approved for human use, key insights were derived from pre-clinical and clinical studies on HAPs of earlier generations. On this basis, Convert’s lead compound was rationally designed as a nitroaromatic analogue with highly optimized drug-like properties.