临床试验中的含硼候选药物

Boron has emerged as a versatile element in medicinal chemistry because its empty p-orbital enables reversible covalent interactions with biologically important nucleophiles while supporting diverse, tunable molecular architectures. Following approval of bortezomib in 2003, boron-containing therapeutics have expanded beyond proteasome inhibition to infectious disease, inflammation, thrombosis, metabolic and cardiovascular disease, cancer immunotherapy, and boron neutron capture therapy (BNCT). This chapter critically surveys boron-containing candidates that have entered clinical trials, organizing them by scaffold class: boronic acids, borinic acids, benzoxaboroles, cyclic boron heterocycles, and boron clusters. The agents reviewed include borofalan, delanzomib, flovagatran, dutogliptin, talabostat, numidargistat, OATD-02, AN0128, epetraborole, ganfeborole, acoziborole, taniborbactam, xeruborbactam, and sodium borocaptate, as well as the five FDA-approved boroncontaining drugs (bortezomib, ixazomib, crisaborole, tavaborole, vaborbactam). Their mechanisms, pharmacokinetics, clinical efficacy, safety, regulatory status, and development trajectories are compared. Collectively, the clinical evidence illustrates how boron chemistry enables selective target engagement through reversible covalent inhibition, tRNA trapping, β-lactamase blockade, arginase modulation, and isotope-mediated cellular destruction. Particularly notable advances include borofalan-based BNCT for head and neck cancer, single-dose acoziborole for gambiense human African trypanosomiasis, ganfeborole-containing regimens for tuberculosis, and broad-spectrum cyclic boronate β-lactamase inhibitors designed to restore antibiotic activity against multidrug-resistant Gram-negative pathogens. Across programs, most candidates were generally well tolerated, whereas discontinuations frequently reflected inadequate comparative efficacy, commercial competition, funding limitations, or manufacturing requirements rather than intrinsic boron toxicity. The histories of dutogliptin and talabostat further demonstrate that mechanistically distinctive boron compounds may be successfully repositioned after setbacks in their original indications. Together, these findings show that boron's structural versatility, low inherent toxicity, and capacity for precise, often reversible target binding continue to support productive clinical translation. The review also highlights how clinical success depends on matching pharmacology with unmet need, feasible administration, competitive differentiation, and durable development partnerships. Ongoing advances in scaffold design, delivery, combination therapy, and indication selection are expected to broaden the therapeutic impact of boron-containing medicines.