Universitéde Strasbourg

Centre National De La Recherche Scientifique

Nexgenix Pharmaceuticals, Inc.

Centre National De La Recherche Scientifique-cnrs

Université Louis Pasteur De Strasbourg

Le Centre National De La Recherche Scientifique

Karplus, Martin

Winssinger, Nicolas

Barluenga, Sofia

Martin Karplus

Nicolas Winssinger

Sofia Barluenga

Jin-Chen Yu

Ruihong Chen

Allan E Rubenstein

John C Chabala

Allan Rubenstein

James Heck

Disclosed are macrocyclic compounds of formulae I, I', II, II&#x2032;, III, III&#x2032;, IV, and V, which are analogs of the pochonin resorcylic acid lactones, pharmaceutical compositions comprising the compounds, and methods and uses comprising the compounds for the treatment of diseases mediated by kinases and Heat Shock Protein 90 HSP90.

Synthesis of resorcylic acid lactones useful as therapeutic agents

A method for identifying one or several molecular structure(s) having a high-affinity for a target of interest, the molecular structure(s) each including one nucleotide chain onto which is hybridized at least one PNA-encoded molecule.

Method of preparing an adduct

Disclosed are novel analogues of the natural product radicicol A of formulae I, .Ia, pi, Ha, lib and HI, pharmaceutical compositions comprising the compounds. The compounds of the invention are kinase and phosphatase inhibitors and find utility in the treatment or prevention of kinase and phosphatase-mediated disorders. Also provided are uses and methods for the treatment or prevention of kinase- and phosphatase-mediated disorders and synthetic processes for the preparation of the compounds. 

Compositions and methods comprising analogues of radicicol A

Disclosed are macrocyclic compounds of formulae I-V, which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.

Macrocyclic compounds useful as inhibitors of kinases and HSP90

The present invention provides compounds of formulae Ia, Ia', IIa, IIa&#x2032;, IIIa, IIIa&#x2032;, IVa, or Va and the therapeutic use thereof. The present invention also includes methods of treating NF2-deficient or NF1-deficient cells or neurodegenerative diseases with radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia&#x2032;, IIa, IIa&#x2032;, IIIa, IIIa&#x2032;, IVa, or Va. Furthermore, the present invention is directed to methods of inhibiting the growth of NF2-deficient or NF1-deficient tumors. The methods comprise contacting NF2-deficient or NF1-deficient tumor cells with radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia&#x2032;, IIa, IIa&#x2032;, IIIa, IIIa&#x2032;, IVa, or Va. The present invention is also directed to the combinational use of radicicol or its derivatives, such as one or more compounds of formula I, II, III, IV, V, Ia, Ia&#x2032;, IIa, IIa&#x2032;, IIIa, IIIa&#x2032;, IVa, or Va with at least one additional active agent, such as one or more HSP90 inhibitors.

Treatment of neurofibromatosis with radicicol and its derivatives

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Strasbourg, France

Sofia Barluenga