Bisphosphonate compounds and methods with enhanced potency for multiple targets including FPPS, GGPPS, and DPPS

摘要

The disclosure provides, inter alia, novel bisphosphonate compounds and m ethods of making and using such compounds. In certain embodiments, compounds of the invention include bisphosphonates that are capable of selectively in hibiting one or more of farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS), and decaprenyl pyrophosphate synthase (DPPS). In preferred embodiments, compounds of the invention are capable of selecti vely inhibiting two or more of FPPS, GGPPS, and DPPS. In embodiments, compou nds and methods of the invention demonstrate superior activity levels, such as in the anti-cancer context, immunostimulation context, and other contexts , which in several cases exceed the activity levels of previous generation b isphosphonate drugs by orders of magnitude. In embodiments, the invention pr ovides compounds and methods in connection with research and therapeutic app lications, e.g., for tumor or cancer cell growth inhibition, activation of g ammadelta T cells, inhibition of certain enzymes related to the mevalonate m etabolic pathway, bone resorption diseases, cancer, immune disorders, immuno therapy, and infectious diseases.