Jean-Yves Winum

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Carbonic anhydrase IX (CAIX) is a hypoxia and HIF-1-inducible protein that regulates intra- and extracellular pH under hypoxic conditions and promotes tumor cell survival and invasion in hypoxic microenvironments. Interrogation of 3,630 human breast cancers provided definitive evidence of CAIX as an independent poor prognostic biomarker for distant(More)
Carbonic anhydrase IX (CAIX) is a hypoxia-inducible enzyme that is overexpressed by cancer cells from many tumor types, and is a component of the pH regulatory system invoked by these cells to combat the deleterious effects of a high rate of glycolytic metabolism. CAIX functions to help produce and maintain an intracellular pH (pHi) favorable for tumor(More)
The zinc enzymes carbonic anhydrases (CAs, EC 4.2.1.1) are very efficient catalysts for the reversible hydration of carbon dioxide to bicarbonate and hence play an important physiological role. In humans, 16 different isozymes have been described, some of them being involved in various pathological disorders. Several of these isozymes are considered as drug(More)
Sulfonamides inhibit the catalytic activity of carbonic anhydrases (CAs, EC 4.2.1.1), enzymes participating in the regulation of acid-base balance and ion transport in many tissues. Carbonic anhydrase IX (CA IX), a transmembrane isoform with predominant association with tumors and limited distribution in normal tissues, is strongly overexpressed by hypoxia.(More)
A panel of compounds belonging to the underexposed sulfamate class of carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was generated that displayed high specificity at nanomolar levels for the tumor-associated CA IX/XII isoforms. Three of the specific CA IX/XII inhibitors showed a positive response in in vitro assays for tumor cell migration and spreading.(More)
A series of 7-substituted coumarins incorporating various glycosyl moieties were synthesized and investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These coumarins were very weak or ineffective as inhibitors of the housekeeping, off target isoforms CA I and II, but some of them inhibited tumor-associated CA IX and XII in(More)
A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on the complex of hCA II with the lead(More)
BACKGROUND AND PURPOSE Carbonic anhydrase IX (CAIX) plays an important role in pH regulation processes critical for tumor cell growth and metastasis. We hypothesize that a dual targeting bioreductive nitroimidazole based anti-CAIX sulfamide drug (DH348) will reduce tumor growth and sensitize tumors to irradiation in a CAIX dependent manner. MATERIAL AND(More)
A series of sulfamates or bis-sulfamates incorporating aliphatic, aromatic, polycyclic (steroidal), and sugar moieties in their molecules has been synthesized and assayed as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more precisely of the cytosolic isozymes CA I andII, and the transmembrane, tumor-associated isozymes CA IX. Some of these(More)
Lipoic acid moieties were attached to amine or amino acids showing activating properties against the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The obtained lipoic acid conjugates of histamine, L-histidine methyl ester, and L-carnosine methyl ester were attached to gold nanoparticles (NPs) by reaction with Au(III) salts in reducing conditions. The CA(More)