Why are we targeting agents for BNCT?

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic cancer treatment that has shown great promise in clinical trials, in which a drug containing 10B atoms is selectively transported into tumor cells and then irradiated with thermal neutrons. It is well known that MMP enzymes including gelatinases MMP-2 and MMP-9 are upregulated in tumors, and these MMPs are responsible for remodeling, angiogenesis, and metastasis, therefore MMPs have been targeted as tumoristatic agents that show excellent efficacy in animal models and have been explored in the clinic for the treatment of cancer. We selected to append a borane-rich carborane cluster onto an MMP-targeting pharmacophore to enable delivery of 10B atoms into a tumor. The piperidine α-sulfone hydroxamate pharmacophore of MMP inhibitors SC-76276, SC-78080, and SC-77964 was selected, as this series of compounds is potent for the desired target MMP enzymes and sparing of MMP-1, and display excellent pharmacokinetic properties.