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Your search keyword '"Coudé, Marie"' showing total 2 results
Start Over Author "Coudé, Marie" Topic acetanilides
2 results on '"Coudé, Marie"'

1. Insights into the cellular pharmacological properties of the BET-inhibitor OTX015/MK-8628 (birabresib), alone and in combination, in leukemia models.

Author

Astorgues-Xerri L, Vázquez R, Odore E, Rezai K, Kahatt C, Mackenzie S, Bekradda M, Coudé MM, Dombret H, Gardin C, Lokiec F, Raymond E, Noel K, Cvitkovic E, Herait P, Bertoni F, and Riveiro ME

Subjects
Animals, Apoptosis drug effects, Biomarkers, Tumor, Cell Cycle drug effects, Cell Line, Tumor, Disease Models, Animal, Drug Synergism, Humans, Mice, Mutation, Xenograft Model Antitumor Assays, Acetanilides pharmacology, Antineoplastic Agents pharmacology, Heterocyclic Compounds, 3-Ring pharmacology, Proteins antagonists & inhibitors
Published
2019
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2. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells.

Author

Coudé MM, Braun T, Berrou J, Dupont M, Bertrand S, Masse A, Raffoux E, Itzykson R, Delord M, Riveiro ME, Herait P, Baruchel A, Dombret H, and Gardin C

Subjects
Apoptosis drug effects, Cell Cycle drug effects, Cell Cycle Proteins, Cell Line, Tumor, Female, Fluorescent Antibody Technique, Humans, Immunoblotting, Male, Nuclear Proteins drug effects, Oligonucleotide Array Sequence Analysis, Protein Serine-Threonine Kinases drug effects, Proto-Oncogene Proteins c-myc drug effects, RNA-Binding Proteins drug effects, Real-Time Polymerase Chain Reaction, Transcription Factors drug effects, Transcriptome, Acetanilides pharmacology, Antineoplastic Agents pharmacology, Heterocyclic Compounds, 3-Ring pharmacology, Leukemia pathology, Nuclear Proteins biosynthesis, Protein Serine-Threonine Kinases biosynthesis, Proto-Oncogene Proteins c-myc biosynthesis, Transcription Factors biosynthesis
Abstract

The bromodomain (BRD) and extraterminal (BET) proteins including BRD2, BRD3 and BRD4 have been identified as key targets for leukemia maintenance. A novel oral inhibitor of BRD2/3/4, the thienotriazolodiazepine compound OTX015, suitable for human use, is available. Here we report its biological effects in AML and ALL cell lines and leukemic samples. Exposure to OTX015 lead to cell growth inhibition, cell cycle arrest and apoptosis at submicromolar concentrations in acute leukemia cell lines and patient-derived leukemic cells, as described with the canonical JQ1 BET inhibitor. Treatment with JQ1 and OTX15 induces similar gene expression profiles in sensitive cell lines, including a c-MYC decrease and an HEXIM1 increase. OTX015 exposure also induced a strong decrease of BRD2, BRD4 and c-MYC and increase of HEXIM1 proteins, while BRD3 expression was unchanged. c-MYC, BRD2, BRD3, BRD4 and HEXIM1 mRNA levels did not correlate however with viability following exposure to OTX015. Sequential combinations of OTX015 with other epigenetic modifying drugs, panobinostat and azacitidine have a synergic effect on growth of the KASUMI cell line. Our results indicate that OTX015 and JQ1 have similar biological effects in leukemic cells, supporting OTX015 evaluation in a Phase Ib trial in relapsed/refractory leukemia patients.

Published
2015
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