Design and Synthesis of Galectin Inhibitors

Sörme, Pernilla; Kahl‐Knutsson, Barbro; Wellmar, Ulf; Magnusson, Bengt-Göran; Leffler, Hakon; Nilsson, Ulf J.

doi:10.1016/s0076-6879(03)01050-4

Cited by 48 publications

(24 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The best galectin-1 inhibitors are o-nitrophenyl thiolactoside (17) or naphtylsulfonyl lactoside (18), and simple p-nitophenyl thiogalactoside (16) extensions seemed to be an attractive strategy for the creation of additional favorable interactions with the protein as well as for the discovery of new high-affinity inhibitors against galectins. Nilsson et al [106,108] thus synthesized 12 new derivatives of LacNAc methyl glycoside (9) by replacing the galactose 3-OH function by amides, sulfonamides and ureas starting from a C'3-azido LacNac compound. These studies revealed that 2 benzamide compounds (19) and (20) were the most active products synthesized, and it was concluded that this replacement was of critical importance for the affinity and inhibitory properties.…”

Section: Modification Of the 3-oh Function Of Galactosementioning

confidence: 99%

Anti-Galectin Compounds as Potential Anti-Cancer Drugs

Ingrassia¹,

Camby²,

Lefranc³

et al. 2006

CMC

View full text Add to dashboard Cite

Galectins form a family of carbohydrate-binding proteins defined by their affinity for beta-galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell migration, three processes that are intimately involved in cancer initiation and progression. Galectins can also display protein-protein types of interactions with their binding partners. Certain galectins directly involved in cancer progression seem to be promising targets for the development of novel therapeutic strategies to combat cancer. Indeed, migrating cancer cells resistant to apoptosis still constitute the principal target for the cytotoxic drugs used to treat cancer patients. Reducing the levels of migration in apoptosis-resistant cancer cells can restore certain levels of sensitivity to apoptosis (and so to pro-apoptotic drugs) in restricted-migration cancer cells. Anti-galectin agents can restrict the levels of migration of several types of cancer cell and should therefore be used in association with cytotoxic drugs to combat metastatic cancer. We provide experimental proof in support of this concept. While the present review focuses on various experimental strategies to impair cancer progression by targeting certain types of galectins, it pays particular attention to glioblastomas, which constitute the ultimate level of malignancy in primary brain tumors. Glioblastomas form the most common type of malignant brain tumor in children and adults, and no glioblastoma patient has been cured to date.

show abstract

Section: Modification Of the 3-oh Function Of Galactosementioning

confidence: 99%

Anti-Galectin Compounds as Potential Anti-Cancer Drugs

Ingrassia¹,

Camby²,

Lefranc³

et al. 2006

CMC

View full text Add to dashboard Cite

show abstract

“…Therefore, several evidences indicate that Galectin-1, which accumulates during tumor progression, represents a relevant mechanism of tumor-mediated immunosuppression and that blockade of this molecule may be helpful for tumor immunotherapy. The possibility to create small molecular inhibitors of Galectin-1 [101] may provide a new class of anti-tumor and immuneenhancing drugs.…”

Section: Immunosuppressive Factors Produced By Tumor Cellsmentioning

confidence: 99%

Targeting Tumor-Related Immunosuppression for Cancer Immunotherapy

Frumento¹,

Piazza²,

Carlo³

et al. 2006

EMIDDT

View full text Add to dashboard Cite

Tumors produce several factors, such as Prostaglandins (PGs), Interleukin (IL)-10, Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor (TGF)-beta, which may directly or indirectly inhibit the immune response and may hamper immunotherapy. Furthermore, cells of innate or adaptive immunity, recruited by tumor-derived factors, may contribute in immunosuppression. Regulatory T (Treg) cells such as the "naturally occurring" CD4(+)/CD25(+) Treg and the IL-10-induced Tr1 cells are major players in this arena. Paradoxically Treg cells are stimulated by IL-2, which is used in tumor immunotherapy. Treg cells suppress T cell responses through soluble factors or by contact-dependent mechanisms, such as the Cytotoxic T Lymphocyte Antigen (CTLA)-4-mediated induction of Indoleamine 2,3-Dioxygenase (IDO) in dendritic cells (DC). IDO inhibits T cell responses by depleting Tryptophan and producing Kynurenine, which is toxic to lymphocytes. Macrophages, granulocytes or myeloid suppressor cells (MSC) suppress immunity by other enzymatic mechanisms, involving Arginase and Nitric Oxide Synthase (NOS). Subversion of tumor immunosuppression is required for successful immunotherapy. Attempts to block or eliminate Treg cells have been made by the use of chemotherapy, anti-CD25 or anti-CTLA-4 antibodies, IL-2-toxin chimeric proteins or Glucocorticoid-induced TNF-like Receptor (GITR) and CD134/OX-40 ligands. Tumor cells genetically modified to secrete IL-21 (an immune-stimulatory "IL-2-like" cytokine, which is not involved in immune regulation) cured experimental metastases in combination with anti-CD25 monoclonal antibodies (mAbs). Also strategies aimed at blocking enzyme-based immune-suppressive mechanisms are suitable, as suggested by experimental evidences in mouse tumor models.

show abstract

“…These include fluorescence polarization (FP) [28], enzyme-linked immunosorbent assay (ELISA) [29], isothermal titration calorimetry (ITC) [30], frontal affinity chromatography (FAC) [31], surface plasmon resonance (SPR) [22], and Gal-3-mediated hemagglutination (G3H) assay [22,23]. However, most of these methods were developed to evaluate small oligosaccharides, and it is unknown whether they can be effectively used to test large pectic polysaccharides.…”

mentioning

confidence: 99%