Discussion
cancers
CANCERS, DISEASE, MINOR, DISORDERS, DISEASES
Galectin-3 inhibitors have been implicated as potential treatments for cancers, fibrotic diseases and other disorders [GB1211 is an α-D-galactopyranoside with high galectin-3 high binding affinity (KFollowing single and multiple oral doses under fasted conditions, GB1211 was absorbed with median TUrinary excretion of unchanged drug represented up to 30% of the administered dose and dosing after a high-fat meal delayed absorption by 2 h but did not markedly affect systemic exposure of GB1211.Systemic exposure to GB1211 increased in a dose-proportional manner across the 5–50 mg (5 mg capsule) dose range, and in a sub-proportional manner across the 50–400 mg (50 mg capsule) dose range. There was a clear difference in exposure between the 5 and 50 mg capsule formulations with a lower systemic exposure and a slightly delayed TIn a recent preclinical study where orally available galectin-3 inhibitors were developed and optimized for the treatment of fibrotic disease, GB1211 was identified as a highly selective galectin-3 inhibitor, with a favorable safety profile against a panel of different targets including enzymes, receptors, and ion channels [Inhibition of galectin-3 with GB1211 was not related to any treatment- or dose-related trends and there were no clinically significant safety or tolerability findings. GB1211 displayed favorable PK properties, with low to moderate variability of systemic exposure and minor food-effect on drug disposition. GB1211 is the first orally bioavailable small molecule galectin-3 inhibitor and is a potential novel treatment for diseases associated with high galectin-3 levels. These findings support further clinical development of GB1211.
