Yeda Research and Develpment & Co. Ltd

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Yoram Shechter

Matityahu Fridkin

Haim Tsubery

Eytan Gershonov

Abraham Shanzer

David Naor

Jacqueline Libman

Itzhak Goldwasher

Reversible pegylated drugs are provided by derivatization of free functional groups of the drug selected from amino, hydroxyl, mercapto, phosphate and/or carboxyl with groups sensitive to mild basic conditions such as 9-fluorenylmethoxycarbonyl (Fmoc) or 2-sulfo-9-fluorenylmethoxycarbonyl (FMS), to which group a PEG moiety is attached. In these pegylated drugs, the PEG moiety and the drug residue are not linked directly to each other, but rather both residues are linked to different positions of the scaffold Fmoc or FMS structure that is highly sensitive to bases and is removable under physiological conditions. The drugs are preferably drugs containing an amino group, most preferably peptides and proteins of low or medium molecular weight. Similar molecules are provided wherein a protein carrier or another polymer carrier replaces the PEG moiety.

Reversible pegylated drugs

The present invention provides a long chain fatty acid (LCFA)-like albumin-binding probe/ligand containing no hydrolysable bond and having an enhanced associating affinity with human serum albumin, which upon conjugation with an amino- or mercapto-containing short-lived drug and administration of the conjugate, significantly prolongs the life time of said drug without substantially interfering with its pharmacological activity. The invention further provides conjugates of said probe with amino- or mercapto-containing drugs, as well as pharmaceutical compositions and uses thereof.

Albumin binding probes and drug conjugates thereof

Disclosed are conjugates of a polypeptide or oligopeptide with a low molecular weight lipophilic compound, the peptide and lipophilic group being covalently linked to one another either directly or via a connecting element, with the exception of (a) conjugates in which the peptide component consists of hirudin or peptide structurally derived from hirudin or a peptide derivative with hirudin-like properties, and (b) conjugates whose peptide component has been hydrophobically modified during their biosynthesis.

Long-acting drugs and pharmaceutical compositions comprising them

Monohydroxamate vanadium complexes of the formula (1): R&mdash;CO&mdash;NHOH.X, wherein R is a residue selected from: (i) H N&mdash;CH(COY)&mdash;(CH ) &mdash;, wherein n is 1, 2 or 3, and Y is OH or NH ; (ii) H N&mdash;CH &mdash;S&mdash;CH &mdash;; and (iii) pyridyl, piperidyl or tetrahydroisoquinolinyl; and X is a vanadium compound selected from a vanadyl (VO ), metavanadate (VO &minus;)or vanadate (VO ) salt, are useful for inducing normoglycemia and/or reducing blood glucose levels in diabetic patients.

Vanadium complexes of monohydroxamates and pharmaceutical compositions comprising them

Tryptophan derivatives substituted by a hydrophobic group, e.g. carbobenzoxy, at the N-terminus, and a hydrophilic group, e.g. --COOH, --SO.sub.3 H or --PO.sub.3 H, at the C-terminus, were found to be cell-permeable blockers of protein tyrosine kinases (PTKs). These PTK blockers are useful in basic research and in the treatment of neoplastic diseases.

Growing community of inventors

Rehovot, Israel

Yoram Shechter