Institut National De La Sante Et De La Recherche Medicale

Université De Bourgogne

Université De Caen Normandie

Daniel Gonzalez

Carmen Garrido Fleury

Anne-Sophie Voisin-chiret

Gaetan Jego

HSP110 inhibitors bind directly to the nucleotide binding domain of HSP110 and then block the phosphorylation of STAT3, cancer cell growth or MyD88 stability. Aspects involve a compound of formula (I) for use in the treatment of a HSP110-associated cancer, for example colorectal cancer and lymphoma. An examplary compound was tested on a syngeneic model for which mouse colon cancer CT-26 cells were injected into Balb/c mice and on a NOD/SCID model in which mice were implanted with human colorectal cancer HCT116 cells. In those animals bearing a tumor, the compound induced tumor regression that was associated with the inhibition of other HSP110 reported tumorigenic functions (resistance to apoptosis, induction of pro-tumor macrophages). Further, the compound was tested on large B cell lymphoma cell lines (DLBCL) and it was able to alter the interaction between HSP110 and MyD88, which induces a degradation of the oncogene MyD88. Additionally, it has been shown that the compound acts synergistically with other anti-cancer agents, including with tyrosine kinase inhibitors like Ibrutinib.

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Dijon, France

Daniel Gonzalez