Use of multivalent synthetic ligands of surface nucleolin for treating cancer or inflammation

• Main Authors: JEAN PAUL BRIAND, YAMINA HAMMA, JOSE COURTY, ARA HOVANESSIAN, GILLES GUICHARD
• Format: Patent
• Language: English
• Published: 19.11.2009
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Use of a polyvalent synthetic ligand (I) to prepare a medicament to treat a disease involving a deregulation of cell proliferation and/or angiogenesis : Use of a polyvalent synthetic ligand (I) of formula [(X) n-Y 1-(Z) i-(Y 2)-(X) m] k-S 1 to prepare a medicament to treat a disease involving a deregulation of cell proliferation and/or angiogenesis. (I) has a support (S 1) on which at least three pseudopeptidic units are grafted, where the bond between Y 1 and Z represents a modified peptide bond, which is significantly more resistant to at least a protease as a standard peptide bond. X : amino acid; Y 1, Y 2amino acid side chain having a basic side chain; Z : proline (preferred) (optionally substituted OH, NH 2, 1-10C alkyl, 1-10C alkenyl, 1-10C alkynyl, 5-12C aryl, 5-14C aralkyl or 5-12C heteroaryl (optionally substituted by 1-6 groups e.g. halo, NO 2, OH, 1-4C alkyl, NH 2, CN, trihalomethyl, 1-4C acyloxy, 1-4C dialkylamino, guanidino or SH)), (un)natural N-alkyl amino acid, dialkyl amino acid, cyclic dialkyl amino acid or pipecolic acid or its derivative; n, i : 0-1, preferably 1; m : 0-3; k : greater than or equal to 3, preferably 5-6; and S 1support. Provided that when Y 1 is arginine then Y 2 is lysine or vice versa. An independent claim is included for a screening process of inhibiting molecules that are involving cell proliferation and angiogenesis comprising placing cells expressing the nucleoline of surface with a molecule to be tested, and determining the ability of the molecule to be tested to be linked with RGG domain of the nucleoline. ACTIVITY : Angiogenesis inhibitor; Cytostatic; Antiinflammatory; Respiratory-Gen.; Immunosuppressive; Antibacterial; Cardiant; Vulnerary; Gastrointestinal-Gen.; Dermatological; Antiallergic. MECHANISM OF ACTION : None given.