Abstract: A method of treating a subject in need of therapy for a condition involving detrimental activity of the enzyme core 2 GlcNAc-T is provided, comprising administration of a therapeutically effective amount of an inhibitor of core 2 GlcNAc-T of formula I to a patient in need thereof wherein: R1 is H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 alkoxy or C1-6-alkoxy-C1-6-alkyl; R2 is H, —OH or C1-6 alkoxy; S1 and S2 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester thereof.

Abstract: Treatments for conditions involving detrimental activity of the enzyme core 2 GlcNAc-T are provided using compounds of the formula I wherein R1 is H, —OH, C1-6 alkoxy, —NR5R6, or Sac 1; R2 is H, —OH, C1-6 alkoxy or Sac 2; R3 is H, —OH, C1-6 alkoxy or Sac 3; R4 is H, C1-6 alkyl, C1-6 hydroxyalkyl or C1-6-alkoxy-C1-6-alkyl; R5 is H, C1-6 alkyl or C1-6 acyl; R6 is H, C1-6 alkyl or C1-6 acyl; Sac 1 Sac 2 and Sac 3 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester form thereof

Abstract: Treatments for conditions involving detrimental activity of the enzyme core 2 GlcNAc-T are provided using compounds of the formula I wherein R1 is H, —OH, C1-6 alkoxy, —NR5R6, or Sac 1; R2 is H, —OH, C1-6 alkoxy or Sac 2; R3 is H, —OH, C1-6 alkoxy or Sac 3; R4 is H, C1-6 alkyl, C1-6 hydroxyalkyl or C1-6-alkoxy-C1-6-alkyl; R5 is H, C1-6 alkyl or C1-6 acyl; R6 is H, C1-6 alkyl or C1-6 acyl; Sac 1 Sac 2 and Sac 3 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester form thereof.

Abstract: A method of treating a subject in need of therapy for a condition involving detrimental activity of the enzyme core 2 GlcNAc-T is provided, comprising administration of a therapeutically effective amount of an inhibitor of core 2 GlcNAc-T of formula I to a patient in need thereof wherein: R1 is H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 alkoxy or C1-6-alkoxy-C1-6-alkyl; R2 is H, —OH or C1-6 alkoxy; S1 and S2 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester thereof.

Abstract: A method of treating a subject in need of therapy for a condition involving detrimental activity of the enzyme core 2 GlcNAc-T is provided, comprising administration of a therapeutically effective amount of an inhibitor of core 2 GlcNAc-T of the formula I to a patient in need thereof wherein R1 is H, —OH, C1-6 alkoxy, —NR5R6, or Sac 1; R2 is H, —OH, C1-6 alkoxy or Sac 2; R3 is H, —OH, C1-6 alkoxy or Sac 3; R4 is H, C1-6 alkyl, C1-6 hydroxyalkyl or C1-6-alkoxy-C1-6-alkyl; R5 is H, C1-6 alkyl or C1-6 acyl; R6 is H, C1-6 alkyl or C1-6 acyl; Sac 1 Sac 2 and Sac 3 are independently selected saccharide moieties, and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester form thereof.

Abstract: The present invention relates to the use of known and novel compounds as inhibitors of UDP-GlcNAc:Gal?1,3GalNAc-R (GlcNAc to GalNAc) ?1,6-N-acetylglucosaminyl transferase (core 2 ?1,6 N-acetylaminotransferase, core 2 GlcNAc-T-EC 2.4.1.102). Such inhibitors have applications in therapy for diseases associated with raised activity of core 2 GlcNAc-T, in particular inflammatory diseases, atherosclerosis, diabetic cardiomyopathy, cancers—including treatment or prevention of metastasis—or diabetic retinopathy.

Abstract: Method of treating conditions associated with raised activity of core 2 GlcNAc-T by administering an inhibitor of UDP-GlcNAc:Gal?1,3GalNAc-R (GlcNAc to GalNAc) ?1,6-N-acetylglucosaminyl transferase (core 2 ?1,6 N-acetylaminotransferase, core 2 GlcNAc-T-EC 2.4.1.102). Diseases associated with raised activity of core 2 GlcNAc-T include inflammatory diseases, atherosclerosis, diabetic cardiomyopathy, cancers, including treatment or prevention of metastasis, or diabetic retinopathy.

Abstract: A method of indicating the presence of the atherosclerosis (particularly coronary artery atherosclerosis) in a subject is provided, comprising comparing the level of Core 2 GlcNAc-T in a tissue sample from a subject with a reference level determined for the same tissue. A level of Core 2 GlcNAc-T in the tissue sample from a subject that is higher than that of the reference level being indicative that the subject is afflicted with atherosclerosis (particularly coronary artery atherosclerosis—coronary artery disease—CAD). In preferred embodiments, the sample consists of leukocytes and the protein level is determined as the enzymatic activity using radiolabeled UDP-GlcNAc and a Gal?(1,3)-GalNAc derivative.

Abstract: Treatments for conditions involving detrimental activity of the enzyme core 2 GlcNAc-T are provided using compounds of the formula I wherein R1 is H, —OH, C1-6 alkoxy, —NR5R6, or Sac 1; R2 is H, —OH, C1-6 alkoxy or Sac 2; R3 is H, —OH, C1-6 alkoxy or Sac 3; R4 is H, C1-6 alkyl, C1-6 hydroxyalkyl or C1-6-alkoxy-C1-6-alkyl; R5 is H, C1-6 alkyl or C1-6 acyl; R6 is H, C1-6 alkyl or C1-6 acyl; Sac 1 Sac 2 and Sac 3 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester form thereof.

Abstract: A method of treating a subject in need of therapy for a condition involving detrimental activity of the enzyme core 2 GlcNAc-T is provided, comprising administration of a therapeutically effective amount of an inhibitor of core 2 GlcNAc-T of the formula I to a patient in need thereof wherein R1 is H, —OH, C1-6 alkoxy, —NR5R6, or Sac 1; R2 is H, —OH, C1-6 alkoxy or Sac 2; R3 is H, —OH, C1-6 alkoxy or Sac 3; R4 is H, C1-6 alkyl, C1-6 hydroxyalkyl or C1-6-alkoxy-C1-6-alkyl; R5 is H, C1-6 alkyl or C1-6 acyl; R6 is H, C1-6 alkyl or C1-6 acyl; Sac 1 Sac 2 and Sac 3 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester form thereof

Abstract: A method of treating a subject in need of therapy for a condition involving detrimental activity of the enzyme core 2 GlcNAc-T is provided, comprising administration of a therapeutically effective amount of an inhibitor of core 2 GlcNAc-T of formula I to a patient in need thereof wherein: R1 is H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 alkoxy or C1-6-alkoxy-C1-6-alkyl; R2 is H, —OH or C1-6 alkoxy; S1 and S2 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester thereof.

Abstract: A method of indicating the presence of the atherosclerosis (particularly coronary artery atherosclerosis) in a subject is provided, comprising comparing the level of Core 2 GlcNAc-T in a tissue sample from a subject with a reference level determined for the same tissue. A level of Core 2 GlcNAc-T in the tissue sample from a subject that is higher than that of the reference level being indicative that the subject is afflicted with atherosclerosis (particularly coronary artery atherosclerosis—coronary artery disease—CAD). In preferred embodiments, the sample consists of leukocytes and the protein level is determined as the enzymatic activity using radiolabeled UDP-GlcNAc and a Gal?(1,3)-GalNAc derivative.

Abstract: The present invention relates to the use of known and novel compounds as inhibitors of UDP-GlcNAc:Gal?1,3GaINAc-R (GlcNAc to GalNAc) ?1,6-N-acetylglucosaminyl transferase (core 2 ?1,6 N-acetylaminotransferase, core 2 GlcNAc-T-EC 2.4.1.102). Such inhibitors have applications in therapy for diseases associates with raised activity of core 2 GlcNAc-T, in particular inflammatory diseases, atherosclerosis, diabetic cardiomyopathy, cancers—including treatment or prevention of metastasis—or diabetic retinopathy.

Abstract: Treatments for conditions involving detrimental activity of the enzyme core 2 GlcNAc-T are provided using compounds of the formula I wherein R1 is H, —OH, C1-6 alkoxy, —NR5R6, or Sac 1; R2 is H, —OH, C1-6 alkoxy or Sac 2; R3 is H, —OH, C1-6 alkoxy or Sac 3; R4 is H, C1-6 alkyl, C1-6 hydroxyalkyl or C1-6-alkoxy-C1-6-alkyl; R5 is H, C1-6 alkyl or C1-6 acyl; R6 is H, C1-6 alkyl or C1-6 acyl; Sac 1 Sac 2 and Sac 3 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester form thereof.

Abstract: A method of treating a subject in need of therapy for a condition involving detrimental activity of the enzyme core 2 GlcNAc-T is provided, comprising administration of a therapeutically effective amount of an inhibitor of core 2 GlcNAc-T of the formula I to a patient in need thereof wherein R1 is H, —OH, C1-6 alkoxy, —NR5R6, or Sac 1; R2 is H, —OH, C1-6 alkoxy or Sac 2; R3 is H, —OH, C1-6 alkoxy or Sac 3; R4 is H, C1-6 alkyl, C1-6 hydroxyalkyl or C1-6-alkoxy-C1-6-alkyl; R5 is H, C1-6 alkyl or C1-6 acyl; R6 is H, C1-6 alkyl or C1-6 acyl; Sac 1 Sac 2 and Sac 3 are independently selected saccharide moieties, and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester form thereof.

Abstract: A method of treatment of Multiple Sclerosis in a subject is disclosed comprising administering to the subject a compound capable of reducing the activity of Core 2 GlcNAc-T. Also disclosed is a method of diagnosing Multiple Sclerosis in a subject and a method of determining the utility of a test substance for use in the treatment of Multiple Sclerosis comprising determining the ability of the substance to inhibit the activity of Core 2 GlcNAc-T.

Abstract: A method of treating a subject in need of therapy for a condition involving detrimental activity of the enzyme core 2 GlcNAc-T is provided, comprising administration of a therapeutically effective amount of an inhibitor of core 2 GlcNAc-T of formula I to a patient in need thereof wherein: R1 is H, C1-6 alkyl, C1-6 hydroxyalkyl, C1-6 alkoxy or C1-6-alkoxy-C1-6-alkyl; R2 is H, —OH or C1-6 alkoxy; S1 and S2 are independently selected saccharide moieties; and Z is a steroid moiety; or a pharmaceutically acceptable salt, ether or ester thereof.