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A GPC3-targeting Bispecific Antibody, GPC3-S-Fab, with Potent Cytotoxicity
Published on: July 12, 2018
Development and Characterization of a High-Affinity Selective Galectin-3 Mouse Tool Compound in Mouse Models of
Kristoffer Peterson1, Ulf J Nilsson1,2, Lise Gravelle3
1Galecto Biotech AB, Sahlgrenska Science Park, Medicinaregatan 8 A, SE-413 46 Gothenburg, Sweden.
Abstract:
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.
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