2. Academic Validation
  3. Development and Characterization of a High-Affinity Selective Galectin-3 Mouse Tool Compound in Mouse Models of Cancer

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

  • J Med Chem. 2024 Dec 26;67(24):21905-21915. doi: 10.1021/acs.jmedchem.4c01747.
Kristoffer Peterson 1,  Ulf J Nilsson 1 2,  Lise Gravelle 3,  Ian Holyer 4,  Karl Jansson 5,  Barbro Kahl-Knutson 6,  Hakon Leffler 6,  Alison C MacKinnon 7,  James A Roper 4,  Robert J Slack 4,  Henrik von Wachenfeldt 5,  Anders Pedersen 3,  Fredrik R Zetterberg 1
Affiliations

Affiliations

  • 1 Galecto Biotech AB, Sahlgrenska Science Park, Medicinaregatan 8 A, SE-413 46 Gothenburg, Sweden.
  • 2 Department of Chemistry, Lund University, Box 124, SE-221 00 Lund, Sweden.
  • 3 Galecto Biotech AB, Cobis Science Park, Ole Maaloes Vej 3, DK-2200, Copenhagen, Denmark.
  • 4 Galecto Biotech ApS, Stevenage Bioscience Catalyst, Stevenage, Hertfordshire SG1 2FX, U.K.
  • 5 Red Glead Discovery AB, Medicon Village, SE-223 63, Lund, Sweden.
  • 6 Department of Laboratory Medicine, Lund University, Box 124, SE-221 00, Lund, Sweden.
  • 7 Galecto Biotech ApS, Nine Edinburgh Bioquarter, 9 Little France Road, Edinburgh EH16 4UX, U.K.
PMID: 39668131 DOI: 10.1021/acs.jmedchem.4c01747
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-170510
    Galectin-3 Inhibitor