1499097-23-2Relevant academic research and scientific papers
A Novel Covalent mTOR Inhibitor, DHM25, Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer Cells
Fouqué, Amélie,Delalande, Olivier,Jean, Mickael,Castellano, Rémy,Josselin, Emmanuelle,Malleter, Marine,Shoji, Kenji F.,Hung, Mac Dinh,Rampanarivo, Hariniaina,Collette, Yves,Van De Weghe, Pierre,Legembre, Patrick
, p. 6559 - 6573 (2015)
Constitutive activation of the PI3K/mTOR signaling pathway contributes to carcinogenesis and metastasis in most, if not all, breast cancers. From a chromene backbone reported to inhibit class I PI3K catalytic subunits, several rounds of chemical syntheses led to the generation of a new collection of chromologues that showed enhanced ability to kill PI3K-addicted cancer cells and to inhibit Akt phosphorylation at serine 473, a hallmark of PI3K/mTOR activation. This initial screen uncovered a chromene designated DHM25 that exerted potent antitumor activity against breast tumor cell lines. Strikingly, DHM25 was shown to be a selective and covalent inhibitor of mTOR using biochemical and cellular analyses, modeling, and a large panel of kinase activity assays spanning the human kinome (243 kinases). Finally, in vivo, this novel drug was an efficient inhibitor of growth and metastasis of triple-negative breast cancer cells, paving the way for its clinical application in oncology. (Figure Presented).
New PI3K/AKT/mTOR inhibitors and pharmaceutical uses thereof
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Paragraph 0096; 0099, (2015/04/15)
The invention relates to new PI3K/AKT/mTOR inhibitors of formula (I) and their use for the prevention and/or the treatment of a disease selected from the group consisting of: inflammatory diseases, autoimmune diseases, neurodegenerative diseases, cancers, transplant rejection, diseases characterized by a premature aging and tuberous sclerosis.
