Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Instituto Di Ricerche Di Biologia Molecolare P. Angeletti

Istituto Di Richerche Di Biologia Molecolare P. Angeletti S.p.a.

Instituto Di Recerche Di Biologia Molecolare P. Angeletti S.p.a.

Istituto Di Richerche Di Biologia Molecolare Di Angeletti S.p.a.

Ralph Laufer

Annalise Di Marco

Isabelle Gloaguen

Riccardo Cortese

Gennaro Ciliberto

Anna De Martis

Domenico Lazzaro

Giacomo Paonessa

Isabella Saggio

Anna Demartis

Patrizia Costa

Ashok Chaudhary

A Rapid And Sensitive Radiometric Assay For Assessing The Activity Of Cytochrome P-450 (CYP) 2C9 And The Potential Of An Analyte To Inhibit CYP2C9 Activity Or Induce CYP2C9 Expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.

Assay for cytochrome P450 isoform 2C9

The present invention relates to methods for screening for anti-obesity agents using the ciliary neutrophic factor receptor.

Method of screening for anti-obesity agents using ciliary neutrophic factor receptor

The variants of human ciliary neutrophic factor (hCNTF) according to the present invention are characterized by substitution of phenylalanine 152 and/or lysine 155 with alanine. These variants have biological properties that render them important as the active principles of drugs for the treatment of diseases and pathologies involving the nervous system or other pathologies involving cells responding to the CNTF. FIG. shows the results of simulation of haptoglobin secretion from HepG2 cells by CNTF and the variants described in the invention.

Variants of human ciliary neurotrophic factor (hCNTF)

The subject of the present invention are variants of ciliary neurotrophic factor with enhanced receptor selectivity (CNTFR), useful for the treatment of diseases and disorders including motor neuron diseases and muscle degenerative diseases. Another subject of the invention is to provide a method for identifying the above mentioned CNTF variants. The hCNTF variants with the amino acid substitutions in accordance with the present invention, have a reduced ability, as compared to the human CNTF, to elicit biological effects through soluble CNTFR, without affecting its ability to activate membrane-bound neuronal CNTF receptors, thereby improving its therapeutic properties. FIG. 1 shows the reduced CNTFR binding affinity of a CNTF variant according to the invention (IA-CNTF; SEQ ID NO: 2). It is evident that the binding affinity of this variant to the CNTFR is reduced as compared to the wild-type human CNTF molecule.

Variant of ciliary neurotrophic factor and DNA encoding the variant

The present invention refers to the use of hCNTF (human ciliary neurotrophic factor), mutants thereof or other molecules that activate the CNTF receptor, for the preparation of drugs for the treatment of obesity and associated disease, for example hyperglycemia. FIG. shows the anti-obesity effect of hCNTF and leptin on body weight (left panels) and on food intake (right panels) in genetically obese mice and in mice with diet-induced obesity (DIO).

Use of CNTF (ciliary neurotrophic factor) receptor activators for the treatment of obesity

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Rome, Italy

Ralph Laufer