Nigratine as first-in-class dual inhibitor of necroptosis and ferroptosis regulated cell death

DELEHOUZE, C.; COMTE, A.; HAUTEVILLE, M.; GOEKJIAN, P. G.; DIMANCHE-BOITREL, M.-T.; ROUSSELOT, M.; BACH, S.

doi:10.1101/2020.12.15.422885

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bioRxiv · 10.1101/2020.12.15.422885

Nigratine as first-in-class dual inhibitor of necroptosis and ferroptosis regulated cell death

DELEHOUZE, C.·COMTE, A.·HAUTEVILLE, M.·GOEKJIAN, P. G.·DIMANCHE-BOITREL, M.-T.·ROUSSELOT, M.·BACH, S.

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Abstract

Nigratine (also known as 6E11), a natural flavanone derivative, was characterized as highly specific non-ATP competitive inhibitor of RIPK1 kinase, one of the key component of necroptotic cell death signaling. We show here that nigratine inhibited both necroptosis (induced by Tumor Necrosis Factor-) and ferroptosis (induced by glutamate, erastin or RSL3 small chemical compounds) with EC50 in the {micro}M range. Altogether, the data obtained showed that nigratine is the first-in-class dual inhibitor of necroptosis and ferroptosis cell death routes and opened new therapeutic avenues for treating complex necrosis-related diseases.

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DELEHOUZE, C., COMTE, A., HAUTEVILLE, M., GOEKJIAN, P. G., DIMANCHE-BOITREL, M.-T., ROUSSELOT, M., BACH, S.. 2020-12-15. Nigratine as first-in-class dual inhibitor of necroptosis and ferroptosis regulated cell death. https://doi.org/10.1101/2020.12.15.422885

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