Centre National De La Recherche Scientifique

Universitè De Montpellier

Institut Curie

Abivax

Université Montpellier 2 Sciences Et Techniques

Universite Claude Bernard – Lyon1

Centre Leon Berard

University of Dundee

Centre National De La Recherche Scientifique-cnrs

Pierre Roux

Jamal Tazi

Didier Scherrer

Romain Najman

Florence Mahuteau

Gilles Gadea

Carsten Brock

Nathalie Cahuzac

David Grierson

Florence Mahuteau-Betzer

Philippe Fort

Véronique Gire

Nikola Arsic

Aude Garcel

Julien Santo

Noelie Campos

Jean-Christophe Bourdon

Pascale Cohen

Julie Vendrell

Marion De Toledo

Fanny Tomas

Fanny Thomas

Christelle Anguille

Kenneth Fernandes

Peggy Raynaud

Stéphanie Vinot

The present invention is in the field of oncology, and more particularly of cancer stem cells. It relates to a method for producing cancer stem cells based on overexpression of Δ133p53β isoform, Δ133p53γ isoform, or both Δ133p53β and Δ133p53γ isoforms; a method for predicting the risk that treatment with a chemotherapeutic anti-cancer agent induces cancer stem cells in a subject suffering from cancer from a cancer sample of said subject, based on detection of an increase in Δ133p53β isoform, Δ133p53γ isoform, or both Δ133p53β and Δ133p53γ isoforms following chemotherapeutic anti-cancer treatment; to therapeutic uses of a combination of chemotherapeutic anti-cancer agent and an agent reducing Δ133p53β isoform, Δ133p53γ isoform, or both Δ133p53β and Δ133p53γ isoforms expression; and also to screening methods for anti-cancer stem cells agents.

Delta133P53Beta and Delta133P53Gamma isoforms are biomarkers of cancer stem cells

A compound of formula (I): wherein A and A' independently represent a phenylene group or a pyridylene group; Ris a hydrogen atom or a (C-C)alkyl group; Ris a 2-pyridyl group, 3-pyridyl group, a 4-pyridyl group, a 2-pyrimidinyl group, a 4-pyrimidinyl group or a 5-pyrimidinyl group; Ris a carbonyl group or a sulfonyl group; and Ris a &#x2014;NH&#x2014;(CH)&#x2014;NRRgroup or a 4-methylpiperazinyl group, with a being an integer from 1 to 4, Rand Rrepresenting independently a (C-C)alkyl group, or Rand Rtogether with the nitrogen atom to which they are linked forming a heterocycle group which is chosen among a 4-methylpiperazinyl group, a morpholino group, a pyrrolidinyl group and a piperidino group; or any one of its pharmaceutically acceptable salt.

Compounds useful for treating cancer

The present invention is in the field of oncology, and more particularly of cancer stem cells. It relates to a method for producing cancer stem cells based on overexpression of &#x394;133&#x3c1;536 isoform, &#x394;133&#x3c1;53&#x3b3; isoform, or both &#x394;133&#x3c1;536 and &#x394;133&#x3c1;53&#x3b3; isoforms; a method for predicting the risk that treatment with a chemotherapeutic anti-cancer agent induces cancer stem cells in a subject suffering from cancer from a cancer sample of said subject, based on detection of an increase in &#x394;133&#x3c1;536 isoform, &#x394;133&#x3c1;53&#x3b3; isoform, or both &#x394;133&#x3c1;536 and &#x394;133&#x3c1;53&#x3b3; isoforms following chemotherapeutic anti-cancer treatment; to therapeutic uses of a combination of chemotherapeutic anti-cancer agent and an agent reducing &#x394;133p536 isoform, &#x394;133&#x3c1;53&#x3b3; isoform, or both &#x394;133&#x3c1;536 and &#x394;133&#x3c1;53&#x3b3; isoforms expression; and also to screening methods for anti-cancer stem cells agents.

Delta133p53beta and delta133p53gamma isoforms are biomarkers of cancer stem cells

The present invention is in the field of stem cells. Particularly, the present invention relates to a reprogramming method for producing induced pluripotent stem cells (iPSC) by transducing somatic differentiated cells with a viral vector expressing &#x394;133p53&#x3b2; isoform, &#x394;133p53&#x3b3; isoform or both &#x394;133p53&#x3b2; and &#x394;133p53&#x3b3; isoforms; to induced pluripotent stem cells as produced by this method; to uses thereof in cell therapy and as an in vitro model for studying various diseases; and to a method for detecting iPSC.

Reprogramming method for producing induced pluripotent stem cells (iPSC)

The present invention relates to a compound of formula (I):  wherein A and A' independently represent a phenylene group or a pyridylene group; Ris a hydrogen atom or a (C-C)alkyl group; Ris a 2-pyridyl group, 3-pyridyl group, a 4-pyridyl group, a 2-pyrimidinyl group, a 4-pyrimidinyl group or a 5-pyrimidinyl group; Ris a carbonyl group or a sulfonyl group; and Ris a &#x2014;NH&#x2014;(CH)&#x2014;NRRgroup or a 4-methylpiperazinyl group, with a being an integer from 1 to 4, Rand Rrepresenting independently a (C-C)alkyl group, or Rand Rtogether with the nitrogen atom to which they are linked forming a heterocycle group which is chosen among a 4-methylpiperazinyl group, a morpholino group, a pyrrolidinyl group and a piperidino group; or any one of its pharmaceutically acceptable salt.

Compounds and pharmaceutically acceptable salts thereof that may be used to treat a disease, for example, Duchenne muscular dystrophy, AIDS, and progeria. The compounds and pharmaceutically acceptable salts thereof may be part of a pharmaceutical composition including a pharmaceutically acceptable support.

Chemical molecules that inhibit the slicing mechanism for treating diseases resulting from splicing anomalies

The present disclosure relates to compound (I) wherein R1 and R2 independently represent a hydrogen atom, a (C-C)alkoxy group, a fluoro(C-C)alkoxy group, a hydroxyl group, a benzyloxy group, a di(C-C)alkylamino group, a pyridyl-vinyl group, a pyrimidinyl-vinyl group, a styryl group, or a &#x2014;NHCOphenyl group; R3, R4 and R5 independently represent a hydrogen atom, a (C-C)alkyl group, a CONHR6 group, a &#x2014;CONR7R8 group, a &#x2014;SONHR6 group, or a heteroaryl group optionally substituted by a halogen atom, a &#x2014;(CH)NR7R8 group or a hydroxy(C-C)alkyl group; R6 represents a hydrogen atom, a &#x2014;(CHR9)(CH)NR7R8 group or a (C-C)alkyl group optionally substituted by a hydroxyl group; or anyone of its pharmaceutically acceptable salt, for use in a method for preventing, inhibiting or treating a disease in a patient suffering thereof, said disease involving a deregulated p53. Some of said compounds are new and also form part of the disclosure.

Compounds for use as therapeutic agents affecting P53 expression and/or activity

The manufacture and use of compounds of formula (Ia) or a pharmaceutically acceptable salt thereof for preventing, inhibiting or treating cancer, AIDS and/or premature aging. The compounds of formula (Ia) being: where:

Compounds for preventing, inhibiting, or treating cancer, AIDS and/or premature aging

A method of treating a disease selected from the group consisting of cancer, Duchenne muscular dystrophy, AIDS, and progeria, that includes administering to a patient in need thereof an effective quantity of at least one compound of formula (IV) or a pharmaceutically acceptable salt thereof.

The present invention relates to a compound of formula (I): wherein A and A' independently represent a phenylene group or a pyridylene group; Ris a hydrogen atom or a (C-C)alkyl group; Ris a 2-pyridyl group, 3-pyridyl group, a 4-pyridyl group, a 2-pyrimidinyl group, a 4-pyrimidinyl group or a 5-pyrimidinyl group; Ris a carbonyl group or a sulfonyl group; and Ris a &#x2014;NH&#x2014;(CH)&#x2014;NRRgroup or a 4-methylpiperazinyl group, with a being an integer from 1 to 4, Rand Rrepresenting independently a (C-C)alkyl group, or Rand Rtogether with the nitrogen atom to which they are linked forming a heterocycle group which is chosen among a 4-methylpiperazinyl group, a morpholino group, a pyrrolidinyl group and a piperidino group; or any one of its pharmaceutically acceptable salt.

The present invention relates to compound (I) wherein R1 and R2 independently represent a hydrogen atom, a (C-C)alkoxy group, a fluoro(C-C)alkoxy group, a hydroxyl group, a benzyloxy group, a di(C-C)alkylamino group, a pyridyl-vinyl group, a pyrimidinyl-vinyl group, a styryl group, or a &#x2014;NHCOphenyl group; R3, R4 and R5 independently represent a hydrogen atom, a (C-C)alkyl group, a CONHR6 group, a &#x2014;CONR7R8 group, a &#x2014;SONHR6 group, or a heteroaryl group optionally substituted by a halogen atom, a &#x2014;(CH)NR7R8 group or a hydroxy(C-C)alkyl group; R6 represents a hydrogen atom, a &#x2014;(CHR9)(CH)NR7R8 group or a (C-C)alkyl group optionally substituted by a hydroxyl group; or anyone of its pharmaceutically acceptable salt, for use in a method for preventing, inhibiting or treating a disease in a patient suffering thereof, said disease involving a deregulated p53. Some of said compounds are new and also form part of the invention.

Compounds for use as therapeutic agents affecting p53 expression and/or activity

A method of preventing, inhibiting, or treating cancer that includes contacting a cell with at least one compound of formula (Ia) or a pharmaceutically acceptable salt thereof: where:

Compounds for treating cancer

The present invention relates to a compound of one of the formulas I to XXI; a pharmaceutical composition comprising at least one such compound; and the use of at least one such compound in preparing a drug to treat, in a subject, a genetic disease resulting from at least one splicing anomaly.

The present invention relates to methods for determining the prognosis of a cancer. The methods involve determining the level of expression of the ZNF217 gene in a cancer cell sample or in a tumor sample wherein over-expression of ZNF217 is correlated with likelihood of metastasis and with likelihood of relapse/recurrence of the cancer.

Growing community of inventors

Saint Gely du Fesc, France

Pierre Roux