Eniricerche S.p.a.

Merck Sharp + Dohme Corp.

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Indiana University

Merck + Co., Inc.

Enichem S.p.a

Sclavo Spa

Msd Italia S.r.l.

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.r.l.

Istituto Nazionale Tumori Irccs “Fondazione G. Pascale”

Istituto Di Ricerche Di Biologia Moleculare S.p.a.

Istituto Di Ricerche Di Biologia Molecolare (irbm)

Istituto Di Recerche Di Biologia Molecolare P. Angeletti S.r.l.

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti

Antonello Pessi

Elisabetta Bianchi

Antonio S Verdini

Fabio Bonelli

Paul E Carrington

Adriano Bernardi

Paolo Ingallinella

Anandan Palani

Ravi P Nargund

Qiaolin Deng

Federica Orvieto

Carlo A Nuzzolo

Donald J Marsh

Ranabir Sinha Roy

George J Eiermann

Richard Dennis DiMarchi

Tomi K Sawyer

Yun-Ping Zhou

Yingjun Mu

David L Smiley

Thomas Joseph Tucker

Gennaro Ciliberto

Armin Lahm

Jonathan Wesley Day

Alessia Santoprete

Joseph M Metzger

Chengwei Wu

Brian P Ward

Licia Tomei

Jackson B Gibbs

Giampietro Corradin

Raffaele De Francesco

Romano Di Trapani

Franco Cardinali

Diana Boraschi

Romas Geleziunas

Maria Vincenza Carriero

Daniela Fattori

Christian Steink&uuml;hler

Andrea Urbani

Anna Demartis

Marina Taliani

Frank Narjes

Alessandro Pocai

Elena Capito

Andrew Wallace

Richardo Cortese

Stefano Censini

Katia Bifulco

David Bramhill

Carlo Antonio Nuzzolo

Richard Dimarchi

Antonio Silvio Verdini

Yin-Ping Zhou

Andrea M Peier

Maria A Bednarek

Marco Finotto

Long-acting co-agonists of the glucagon and GLP-1 receptors are described.

Long-acting co-agonists of the glucagon and GLP-1 receptors

The present invention discloses retro-inverso peptides and pharmaceutical composition containing them. The peptides of the invention prevent key events occurring during the metastatic process, i.e. invasion of the extracellular matrix, formation of a capillary network, and the entry into bloodstream. They are therefore useful in the treatment of diseases and conditions that are sustained by an increase of cell motility, cell invasion, and/or angiogenesis, such as tumors and chronic inflammation.

Retro-inverso peptide inhibitors of cell migration, extracellular matrix and endothelial invasion by tumor cells

Co-agonists of the glucagon and GLP-1 receptors are described.

Co-agonists of the glucagon and GLP-1 receptors

Described are peptide analogs of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have relatively balanced agonist activity at the glucagon-like peptide 1 (GLP-1) receptor and the glucagon (GCG) receptor, and the use of such GLP-1 receptor/GCG receptor co-agonists for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.

Peptide analogs of oxyntomodulin (OXM, glucagon-37), which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to act as a dual GLP-1/glucagon receptor (GCGR) agonist are described. The peptide analogs are useful for treatment of metabolic disorders such as diabetes and obesity.

Oxyntomodulin analogs

Modified glucagon peptides are disclosed having enhanced potency at the glucagon receptor relative to native glucagon. Further modification of the glucagon peptides by forming intramolecular bridges or the substitution of the terminal carboxylic acid with an amide group produces peptides exhibiting glucagon/GLP-1 receptor co-agonist activity. The solubility and stability of these high potency glucagon analogs can be further improved by modification of the polypeptides by pegylation, acylation, alkylation, substitution of carboxy terminal amino acids, C-terminal truncation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 26 (GPSSGAPPPS), SEQ ID NO: 27 (KRNRNNIA) and SEQ ID NO: 28 (KRNR).

Glucagon/GLP-1 receptor co-agonists

The present invention relates to compounds comprising at least ten contigous amino acids of the HR2 domain of a Type 1 viral fusogenic protein of an enveloped virus, or a derivative thereof, attached at the C-terminal to cholesterol or a derivative thereof; or a pharmaceutically acceptable salt thereof which inhibit viral fusion. Thus compounds of the invention are useful to prevent or treat diseases caused by an enveloped virus.

Cholesterol derivatives of inhibitors of viral fusion

Modified oxyntomodulin derivatives. Such derivatives can be used for the treatment of metabolic diseases such as diabetes and obesity.

Pharmaceutical composition comprising oxyntomodulin derivatives and a method for reducing body weight using the composition

Methods of covalently-stabilizing alpha-helical, chimeric peptides constrained within a homotrimeric or heterotrimeric coiled-coil structure are disclosed. The coiled-coil structures made by the methods disclosed within this specification mimic all or a portion of the internal, trimeric coiled-coil motif contained within the fusogenic conformation of an enveloped virus membrane-fusion protein, particularly the internal coiled-coil domain of the HIV gp41 ectodomain. The HIV-derived, chimeric peptides disclosed comprise a non-HIV, soluble, trimeric form of a coiled-coil fused in helical phase to all or a portion of the N-helix of HIV gp41 and are covalently-stabilized in a homotrimeric or heterotrimeric coiled-coil structure through the formation of disulfide or chemoselective bonds between said peptides. The covalently-stabilized, HIV-derived, homotrimeric or heterotrimeric coiled-coil structures made by the methods disclosed herein represent a close mimetic of a HIV gp41 fusion intermediate and are potent inhibitors of HIV infectivity. These HIV-derived chimeric peptides may provide for therapeutic treatment against HIV infection by inhibiting the virus-host cell membrane fusion process.

Covalently stabilized chimeric coiled-coil HIV gp41 N-peptides with improved antiviral activity

Compounds of formula (I) and pharmaceutically acceptable salts and esters thereof are active as inhibitors of hepatitis C virus NS3 protease. Consequently they are potentially useful in the treatment and prevention of hepatitis C virus infection and related conditions. In formula: (I) represents an aromatic or aliphatic carbocyclic ring and (n) is the total number of carbon atoms in the ring and is form 4 to 8.

HCV NS3 protease inhibitors

The process according to the present invention allows expression and isolation of polypeptides with the proteolytic activity of HCV NS3 protease in a pure, catalytically active form, and in amounts that are sufficient for discovery of NS3 protease inhibitors and for determination of the three-dimensional structure of the NS3 protease. A further subject of the present invention is a procedure that defines the chemical and physical conditions necessary for completion of the proteolytic activity of the above polypeptides. The invention further comprises new compositions of matter (expression vectors) containing nucleotide sequences capable of expressing the above mentioned polypeptides in culture cells. Finally, new compounds of matter are defined, suitable to measure the above proteolytic activity, and useful to develop NS3 protease inhibitors and therefore therapeutic agents for use against HCV. The figure shows the kinetic parameters of HCV NS3 protease using the S3 depsipeptide substrate (SEQ ID NO:45).

Methodology to produce, and purify and assay polypeptides with the proteolytic activity of the HCV NS3 protease

The present invention is directed to tetrapeptides which inhibit farnesyl-protein transferase (FPTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to a method of treating cancer with tetrapeptide inhibitors of farnesyl protein transferase, as well as pharmaceutical formulations useful for this method of treatment.

Peptide inhibitors of farnesyl-protein transferase

An ELISA method with competitive inhibition is described for determining antisporozoite antibodies of P. Falciparum in human blood samples and in mosquito extract, which uses a single plate pretreated with only the synthetic antigen (NANP).sub.20 using, as total competitive inhibitor for the formation of the complex between the synthetic antigen adsorbed on the plate and the antibody contained in the sample, the (NANP).sub.20 synthetic peptide in a weight ratio of at least 20:1 with respect to the adsorbed antigen. Because of its high specificity, sensitivity and speed, the method is particularly suitable for epidemiological studies on malaria.

Immunoenzymatic single-plate ELISA method with competitive inhibition

Growing community of inventors

Rome, Italy

Antonello Pessi