Nerviano Medical Sciences S.r.l.

Pharmacia & Upjohn

Farmitalia Carlo Erba

Incyte Genomics, Inc.

Farmitalia Carlo Erba S.r.l.

Pharmacia Italia S.p.a.

Pharmacia & Tubjohn Spa

Antonella Isacchi

Paolo Pevarello

Manuela Villa

Daniele Fancelli

Gabriella Traquandi

Anna Vulpetti

Raffaella Amici

Paolo Sarmientos

Rosita Lupi

Michele Modugno

Laura Bergonzoni

Roberta Bosotti

Jens Berthelsen

Chiara Soncini

Luisa Rusconi

Olga Bandman

Mario Varasi

Salvatore Toma

Romeo Roncucci

Jurgen Moll

Guy Mazue

David M Hodgson

Juergen Moll

Simon Plyte

Emanuela Scacheri

Paola Magnaghi

Angela Molteni

Gilles Cauet

The invention provides low molecular weight compounds, namely tetrahydropyrrolo[3,4-c]pyrazoles, showing a high affinity for the ATP pocket of ABL tyrosine kinase. These compounds are thus ATP-competitive tyrosine kinase inhibitors displaying a significant inhibitory potency also, and in particular, towards BCR-ABL inhibitor-resistant T315I ABL mutants. The compounds of the invention find a useful application in the treatment of BCR-ABL inhibitor-resistant ABL-mediated diseases, such as Imatinib-resistant chronic myelogenous leukemia. Moreover, the invention provides a screening method for the identification of compounds capable of binding the ATP pocket of a kinase protein, in particular of the T315I mutant ABL kinase.

Use of a kinase inhibitor for the treatment of particular resistant tumors

The invention provides low molecular weight compounds, namely 1H-thieno[2,3-c]pyrazoles, showing a high affinity for the ATP pocket of ABL tyrosine kinase. These compounds are thus ATP-competitive tyrosine kinase inhibitors displaying a significant inhibitory potency also, and in particular, towards BCR-ABL inhibitor-resistant T315I ABL mutants. The compounds of the invention find a useful application in the treatment of BCR-ABL inhibitor-resistant ABL-mediated diseases, such as Imatinib-resistant chronic myelogenous leukemia. Moreover, the invention provides a screening method for the identification of compounds capable of binding the ATP pocket of a kinase protein, in particular of the T315I mutant ABL kinase.

The present invention provides a human polypeptide homolog of DBF4/ASK1 (for 'Activator of S phase kinase') and polynucleotides which identify and encode DRF1 (for 'DBF4 Related Factor 1'). In addition, the invention provides expression vectors, host cells and methods for its production. The invention also provides methods for the identification of DRF1 or DRF1-containing complex agonists/antagonists, useful for the treatment of human diseases and conditions.

Human homologue of the DBF4/ASK1 protein, nucleic acids, and methods related to the same

Compounds which are 2-amino-1,3-thiazole derivatives of formula (I)wherein R is a halogen atom, a nitro group, an optionally substituted amino group or it is a group, optionally further substituted, selected from i) straight or branched C&#x2013;Calkyl, C&#x2013;Calkenyl or C&#x2013;Calkynyl; ii) C&#x2013;Ccycloalkyl; iii) aryl or arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain; Ris an optionally further substituted group selected from: i) straight or branched C&#x2013;Calkyl or C&#x2013;Calkenyl; ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring; iii) aryl or arylcarbonyl; iv) arylalkyl with from 1 to 8 carbon atoms within the straight or branched alkyl chain; v) arylalkenyl with from 2 to 6 carbon atoms within the straight or branched alkenyl chain; vi) an optionally protected amino acid residue; or a pharmaceutically acceptable salt thereof; are useful for treating cell proliferative disorders associated with an altered cell dependent kinase activity.

2-amino-thiazole derivatives, process for their preparation, and their use as antitumor agents

Compounds which are 2-ureido-1,3-thiazole derivatives of formula (I) wherein R is a halogen atom, a nitro group, an optionally substituted amino group or it is a group optionally further substituted, selected from: i) straight or branched C-Calkyl; ii) C-Ccycloalkyl; iii) aryl or arylalkyl with from 1 to 6 carbon atoms within the straight or branched alkyl chain; Ris an optionally substituted group selected from: i) straight or branched C-Calkyl; ii) 3 to 6 membered carbocycle or 5 to 7 membered heterocycle ring; iii) aryl or arylcarbonyl; iv) arylalkyl with from 1 to 6 carbon atoms within the straight or branched alkyl chain; Ris hydrogen, a straight or branched C-Calkyl or C-Calkenyl or alkynyl group; or, taken together with the nitrogen atom so which they are bonded, Rand Rform a substituted or unsubstituted group selected from: i) an optionally benzocondensed or bridged 5 to 7 membered heterocycle; or ii) a 9 to 11 membered spiro-heterocyclic compound; or a pharmaceutically acceptable salt thereof; are useful for treating cell proliferative disorders associated with an altered cell dependent kinase activity.

2-Ureido-thiazole derivatives, process for their preparation, and their use as antitumor agents

Compounds which are 4,5,6,7-tetrahydroindazole derivative formula (1), wherein the dotted line (x) represents a single or double bond; n is 0 or 1; R , R and R have the meanings reported in the description; Ra, R&prime;a, Rb, R&prime;b, Rc, R&prime;c have the meanings reported in the description, also comprising that Ra and Rb together and/or Ra and Rc together form a N-alkylpiperydinyl ring with 1 to 6 carbon atoms in the alkyl chain or a phenyl ring; or pharmaceutically acceptable salts thereof, are useful for treating cell proliferative disorders and Alzheimer's disease.

4,5,6,7-tetrahydroindazole derivatives as antitumor agents

The invention provides a nucleic acid molecule which encodes the human NIM1 kinase. It also provides for the use of the nucleic acid molecule, fragments, variants and complements thereof and of the protein, portions thereof and antibodies thereto for characterization, diagnosis, evaluation, treatment, or prevention of disorders associated with expression. The invention additionally provides expression vectors and host cells for the production of the protein and a transgenic organism or model system.

Human NIM1 kinase

The present invention provides a human polypeptide homolog of human tankyrase protein (THP) and polynucleotides which identify and encode THP. In addition, the invention provides expression vectors, host cells and methods for its production. The invention also provides methods for the identification of THP agonists/antagonists, useful for the treatment of human diseases, such as human cancer and age related diseases.

Tankyrase homolog protein (THP), nucleic acids, and methods related to the same

The present invention relates to the production, by recombinant DNA techniques, of derivatives of basic fibroblast growth factor (bFGF). These derivatives of bFGF can act as antagonists and/or superagonists of the wild type molecule in the angiogenic process. These derivatives, as well as wild type bFGF, may be prepared by the use of strains or E. coli which have been transformed with plasmids carrying nucleotide sequence coding for human and bovine bFGF and their derivatives.

Deletion mutant of basic fibroblast growth factor and production thereof

The present invention provides a polypeptide which is capable of binding specifically human basic fibroblast growth factor and human acidic fibroblast growth factor, a DNA sequence which encodes the polypeptide of the invention and a vector which incorporates a DNA sequence of the invention and which is capable, when provided in a transformed host, of expressing the polypeptide of the invention encoded by the DNA sequence. A host transformed with such a vector forms part of the invention also.

Extracellular form of the human fibroblast growth factor receptor

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Milan, Italy

Antonella Isacchi