Development and Characterization of a High-Affinity Selective Galectin‑3 Mouse Tool Compound in Mouse Models of Cancer

The interest in galectin-3 as a drug target in the cancer
and fibrosis
space has grown during the past few years with several new classes
of compounds being developed. The first orally available galectin-3
inhibitor, GB1211 (h-galectin-3 Kd = 0.025
μM), is currently in phase 2 clinical trials. Due to structural
differences between human and mouse galectin-3 a significant reduction
in mouse galectin-3 affinity is observed for most highly potent human
galectin-3 inhibitors including GB1211 (m-galectin-3
Kd = 0.77 μM). Pharmacokinetic experiments in mouse
dosing GB1211 up to 100 mg/kg results in free plasma
levels below m-galectin-3 Kd, which is not comparable to
the data observed in humans. To better support translation into clinical
studies, a new improved mouse galectin-3 tool compound, GB2095, was developed. Dosing this new compound in in vivo syngeneic mouse
models of cancer resulted in reduction of the growth of breast and
melanoma cancers.