Development\nand Characterization of a High-Affinity\nSelective Galectin‑3 Mouse Tool Compound in Mouse Models of\nCancer

The interest in galectin-3 as a drug target in the cancer\nand fibrosis\nspace has grown during the past few years with several new classes\nof compounds being developed. The first orally available galectin-3\ninhibitor, <b>GB1211</b> (h-galectin-3 K<sub>d</sub> = 0.025\nμM), is currently in phase 2 clinical trials. Due to structural\ndifferences between human and mouse galectin-3 a significant reduction\nin mouse galectin-3 affinity is observed for most highly potent human\ngalectin-3 inhibitors including <b>GB1211</b> (m-galectin-3\nK<sub>d</sub> = 0.77 μM). Pharmacokinetic experiments in mouse\ndosing <b>GB1211</b> up to 100 mg/kg results in free plasma\nlevels below m-galectin-3 K<sub>d</sub>, which is not comparable to\nthe data observed in humans. To better support translation into clinical\nstudies, a new improved mouse galectin-3 tool compound, <b>GB2095</b>, was developed. Dosing this new compound in in vivo syngeneic mouse\nmodels of cancer resulted in reduction of the growth of breast and\nmelanoma cancers.