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Lactulose as a novel template for anticancer drug development targeting galectins.

Kishor C, Ross RL, Blanchard H
Chem Biol Drug Des 92 1801-1808 (2018)
Cited: 7 times
EuropePMC logo PMID: 29888844

Abstract

Galectins are carbohydrate binding proteins (lectins), which characteristically bind β-galactosides. Galectins play a role in tumour progression through involvement in proliferation, metastasis, angiogenesis, immune evasion and drug resistance. There is need for inhibitors (antagonists) that are specific for distinct galectins and that can interfere with galectin-carbohydrate interactions during cancer progression. Here, we propose that lactulose, a non-digestible galactose-fructose disaccharide, presents a novel inhibitor scaffold for design of inhibitors against galectins. Thermodynamic evaluation displays binding affinity of lactulose against the galectin-1 and galectin-3 carbohydrate recognition domain (CRD). Crystal structures of galectin-1 and galectin-3 in complex with lactulose reveal for the first time the molecular basis of the galectin-lactulose interactions. Molecular modelling was implemented to propose novel lactulose derivatives as potent anti-cancer agents.

Articles - 6b94 mentioned but not cited (1)

  1. Structure-based identification of galectin-1 selective modulators in dietary food polyphenols: a pharmacoinformatics approach. Bhowmick S, Saha A, AlFaris NA, ALTamimi JZ, ALOthman ZA, Aldayel TS, Wabaidur SM, Islam MA. Mol Divers 26 1697-1714 (2022)


Reviews citing this publication (3)

  1. Targeting galectin-driven regulatory circuits in cancer and fibrosis. Mariño KV, Cagnoni AJ, Croci DO, Rabinovich GA. Nat Rev Drug Discov 22 295-316 (2023)
  2. Inhibition of galectins in cancer: Biological challenges for their clinical application. Laderach DJ, Compagno D. Front Immunol 13 1104625 (2022)
  3. The complexity of tumour angiogenesis based on recently described molecules. Wiśniewska W, Kopka M, Siemiątkowska K, Fudalej MM, Sobiborowicz A, Badowska-Kozakiewicz AM. Contemp Oncol (Pozn) 25 33-44 (2021)

Articles citing this publication (3)

  1. Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice. Baek JH, Kim DH, Lee J, Kim SJ, Chun KH. Cell Death Dis 12 66 (2021)
  2. Reduction in Gastrointestinal Cancers in Cirrhotic Patients Receiving Rifaximin vs Lactulose Only Therapy for Hepatic Encephalopathy. Patel AH, Li Y, Minacapelli CD, Catalano K, Rustgi V. Cureus 15 e35259 (2023)
  3. TF-containing MUC1 glycopeptides fail to entice Galectin-1 recognition of tumor-associated Thomsen-Freidenreich (TF) antigen (CD176) in solution. FitzGerald FG, Rodriguez Benavente MC, Garcia C, Rivero Y, Singh Y, Wang H, Fields GB, Cudic M. Glycoconj J 37 657-666 (2020)


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