Dac S.r.l.

Universita′ Degli Studi Di Milano

Università Degli Studi Di Roma "La Sapienza"

Istituto Europeo Di Oncologia S.r.l.

Universitá Degli Studi Di Pavia

Topotarget Germany Ag

Fondazione Ieo

Congenia Slr

Cogenia Srl

Congenia S.r.l.

Saverio Minucci

Mario Varasi

Marco Ballarini

Florian Thaler

Antonello Mai

Giacomo Carenzi

Gilles Pain

Ciro Mercurio

Silvio Massa

Pier Giuseppe Pelicci

Gaetano Gargiulo

Agnese Abate

Daniele Fancelli

Manuela Villa

Anna Cappa

Simon Plyte

Stephen Martin Courtney

Raffaella Amici

Stefania Gagliardi

Christopher John Yarnold

Paolo Bernardi

Andrea Colombo

Andrea Mattevi

Mario Faretta

Seyed Amir Hosseini

PierGiuseppe Pellicci

Marco Giorgio

Joachim Kraemer

Giuseppe Pier Pelicci

Daniele Piccini

Marco Maccarana

Simona Ronzoni

Maria Carmela Fulco

Beatriz Liliana Areces

Piergiuseppe Pelicci

The present disclosure relates to methods of treating cancer and pharmaceutical compositions for use in the treatment of cancer, including LSD1-inhibitor-resistant cancers, comprising administering to a subject an effective amount of a cell cycle inhibitor, such as a CDK4/6 inhibitor or a p21 enhancer, and an effective amount of a LSD1 inhibitor.

Use of a combinational therapy of LSD1 inhibitors with P21 activators in the treatment of cancer

This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; Ris hydrogen; C-Calkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R; (SO)R; cycloalkyl; aryl; or heteroaryl; Ris C-Calkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R; X is CH, oxygen or NR; Y is a bond, CHRor NR; Z is oxygen, CRRor C&#x2550;R; and R, R, R, R, R, R, R, Rand Rare as further defined in the specification; and pharmaceutical acceptable salts thereof. 

Spirocyclic derivatives as histone deacetylase inhibitors

This invention is related to new histone deacetylase inhibitors according to the general formula (I), wherein: m and n are independently zero or an integer from 1 to 4; p is zero or an integer from 1 to 3, with the proviso that when p is zero, n and m cannot be both 1; R is hydrogen; C-Calkyl, optionally substituted by C-Ccycloalkyl, C-Caryl or hetero(C-C)aryl; (CO)R; (SO)R; C-Ccycloalkyl; C-Caryl; or hetero(C-C)aryl; Ris halogen, C-Calkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy; Y is CHor NR; Z is C&#x2550;R; and R, R, R, and Rare as further defined in the specification; and pharmaceutical acceptable salts thereof. 

Tranylcypromine derivatives useful as therapeutic agents, particularly for the prevention and/or treatment of diseases and conditions associated with the activity of histone demethylases LSD1 and LSD2, such as the diseases characterized by deregulation of gene transcription, cell differentiation and proliferation, e.g. tumors, viral infections, are herein described. These compounds belong to the structural formula (I) wherein A and Rare as defined in the specification. The invention also relates to the preparation of these compounds, as well as to compositions containing them and to therapeutic use thereof. 

Tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and/or LSD2

Acrylamido derivatives useful as therapeutic agents, particularly for the prevention and/or treatment of diseases and conditions associated with the activity of the mitochondrial permeability transition pore (MPTP), such as the diseases characterized by ischemia/reperfusion, oxidative or degenerative tissue damage, are herein described. These compounds belong to the structural formula (I) wherein R, R', R&#x2033;, W and a are as defined in the specification. The invention also relates to the preparation of these compounds, as well as to pharmaceutical compositions comprising them. 

Acrylomido derivatives useful as inhibitors of the mitochondrial permeability transition

Acrylamido derivatives useful as inhibitors of the mitochondrial permeability transition

New histone deacetylase inhibitors according to the general formula (I) wherein: Q is a bond, CH, CH&#x2014;NRR, NRor oxygen, X is CH or nitrogen, Y is a bond, CH, oxygen or NR, Z is CH or nitrogen, R, Rare, independently, hydrogen, halogen, C-Calkyl or C-Chaloalkyl, R, Rare, independently, hydrogen or C-Calkyl, and R, R, Rand Rare as further defined in the specification.

Class of histone deacetylase inhibitors

New inhibitors of histone deacetylases having antitumor activity, and the process of preparation thereof are herein described. These compounds belong to the structural formula (I) where Ris a linear or branched chain containing at least two conjugated double bonds, A is an optionally substituted phenyl or pyridyl ring, Ar is an aryl or heteroaryl group, and Ris hydrogen or alkoxyalkyl. The application also describes the use of said compounds in the treatment of diseases associated to the deregulation of histone deacetylases activity, such as tumors, as well as the relevant pharmaceutical compositions for administration to patients requiring said treatment.

Histone deacetylases inhibitors

The invention discloses the use of a compound of formula (I), wherein R, R, R, and Reach independently represents: hydrogen; halo; hydroxy; (C-C) alkyl optionally substituted by hydroxy or (C-C) alkoxy; (C-C) haloalkyl; (C-C) alkoxy; and (C-C) haloalkoxy; for the preparation of a medicament for the prevention and/or treatment of diseases resulting from opening of the MPTP which are characterized by degenerative tissue damages, in particular, diabetes and diabetic complications, neurological diseases and stroke, heart infarction, inherited dystrophies and hepatitis, more particularly, diabetic vascular diseases, such as diabetic retinopathy, and neurodegenerative disorders, such as multiple sclerosis. Further objects are a group of selected individual compounds of formula (I) for use as medicaments and a further group of selected individual compounds of formula (I) as novel compounds. 

Phenyl substituted maleimides as medicaments for blocking degenerative tissue damages by inhibiting MPT

The invention relates to a method for determining whether a treatment of a disorder with an HDAC inhibitor is to be started/continued or not comprising determining the level of histone acetylation in the sample by use of an antibody capable of binding to acetylated histone, and classifying the disorder as to be treated with an HDAC inhibitor when the level of histone acetylation is significantly lower than that of a reference sample. The invention further relates to the diagnostic and prognostic use of specific antibodies and cell lines producing them.

Antibody tools for the diagnostic use in the medical therapy with inhibitors of histone deacetylases

Growing community of inventors

Noverasco di Opera, Italy

Saverio Minucci