Prohibitins

Flavaglines: discovery from plants used in traditional Chinese medicine, synthesis and drug development against cancer and immune disorders. Wang D., Tezeren M., Abou-Hamdan H., Yu P. Nebigil CG., Désaubry L. Curr. Chin.Chem. 1: in press (2021).

Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells. Tortelli T.C., Tamura R.E., de Souza Junqueira M., da Silva Mororó J., Bustos S.O., Natalino R.J.M., Russell S., Désaubry L., Strauss B.E., Chammas R. Aging 13: 21914-21940 (2021).

Prohibitin inactivation in adipocytes results in reduced lipid metabolism and adaptive impairment. Gao Z., Daquinag A.C., Fussell C., Djehal A., Désaubry L., Kolonin M.G. Diabetes 70: 2204-2212 (2021).

Prohibitin, STAT3 and SH2D4A physically and functionally interact in tumor cell mitochondria. Ploeger C., Huth T., Sugiyanto R.N., Pusch S, Goeppert B., Singer S., Tabti R., Hausser I., Schirmacher P., Désaubry L., Roessler S. Cell Death Dis 11: 1023 (2020).

Development of prohibitin ligands against osteoporosis. Tabti R, Lamoureux F, Charrier C, Ory B, Heymann D, Bentouhami E, Désaubry L. Eur. J. Med. Chem. in press (2020).

SFPH proteins as therapeutic targets for a myriad of diseases. Wang D., Tabti R.,  Elderwish S., Djehal A., Chouha N., Pinot F., Nebigil CG., Désaubry L.  Bioorg. Med. Chem. Lett, 30: 127600 (2020). Flavagline synthetic derivative induces senescence in glioblastoma cancer cells without being toxic to healthy astrocytes. Harmouch E., Seitlinger J., Chaddad H., Barths J., Désaubry L., Grandemange S., Massfelder T., Ubeaud-Sequier G., Fuhrmann G., Fioretti F., Benkirane-Jessel N., Idoux-Gillet Y. Sci. Rep. 10: 13750 (2020).

Flavaglines as natural products targeting eIF4A and prohibitins: from traditional Chinese medicine to antiviral activity against coronaviruses. Nebigil CG, Moog C, Vagner S, Benkirane-Jessel N, Smith DR,  Désaubry L.  Eur. J. Med. Chem. 203: 112653 (2020).The synthetic small molecule FL3 combats intestinal tumorigenesis via Axin1 inhibition of Wnt/β-catenin signaling. Jackson DN, Alula KM, Delgado-Deida Y, Tabti R, Turner K, Wang X, Venuprasad K, Souza RF, Désaubry L, Theiss AL. Cancer Res. 80: 3519-3529 (2020). A subset of flavaglines inhibits KRAS nanoclustering and activation. Yurugi H, Zhuang Y, Siddiqui FA, Liang H, Rosigkeit S, Zeng Y, Abou-Hamdan H, Bockamp E, Zhou Y, Abankwa D, Zhao W, Désaubry L, Rajalingam K. J. Cell. Sci. (2020), in press.

The prohibitin-binding compound fluorizoline affects multiple components of the translational machinery and inhibits protein synthesis. Jin X, Xie J, Zabolocki M, Wang X, Jiang T, Wang D, Désaubry L, Bardy C, Proud CG. J. Biol. Chem. 295: 9855-9867 (2020).

Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases. Wang D., Tabti R.,  Elderwish S., Abou-Hamdan H., Djehal A., Yu P., Yurugi H., Rajalingam R., Nebigil CG., Désaubry L. Cell. Mol. Life Sci. 77: i3525-3546 (2020).

Discovery of 3,3’-pyrrolidinyl-spirooxindoles as cardioprotectant prohibitin ligands. Elderwish S., Audebrand A., Nebigil CG, Désaubry L. Eur. J. Med. Chem. 186: 111859 (2020).

Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects. Bentayeb H., Aitamer M., Petit B., Dubanet L., Elderwish S., Désaubry L., de Gramont A., Raymond E., Olivrie A., Abraham J., Jauberteau M-O., Troutaud D.  J. Exp. Clin. Cancer Res. 38: 450 (2019).

Prohibitin 2 promotes PINK1/Parkin-dependent mitophagy by PARL-PGAM5-PINK1 axis. Yan C., Gong L., Li C., Xu M., Abou-Hamdan H., Tang M., Désaubry L., Song Z. Autophagy, 1-16 (2019). doi: 10.1080/15548627.2019.1628520

The synthetic flavagline FL3 spares normal human skin cells from its cytotoxic effect via an activation of Bad. Emhemmed F, Azouaou SA, Hassan S, Lefevbre R, Désaubry L, Muller CD, Fuhrmann G. Toxicol In Vitro. 60: 27-35 (2019).

Targeting prohibitin with small molecules to promote melanogenesis and apoptosis in melanoma cells. Djehal A., Krayem M., Najem A., Hammoud H., Cresteil T., Nebigil, C.G., Wang D., Yu P., Bentouhami E., Ghanem GE., Désaubry L.  Eur. J. Med. Chem. 155: 880-888 (2018).

Flavagline analog FL3 induces cell cycle arrest in urothelial carcinoma cell of the bladder by inhibiting the Akt/PHB interaction to activate the GADD45α pathway.Yuan G-J., Chen X, Liu Z-W.; Wei W-S., Shu Q-H., Abou-Hamdan H., Jiang L-J., Li X-D., Chen R-X.; Désaubry L., Zhou F-J.; Xie D. J. Exp. Clin. Cancer Res. 37: 21 (2018).

The prohibitin-binding compound fluorizoline induces apoptosis in chronic lymphocytic leukemia cells ex vivo but fails to prevent leukemia development in a murine model. Wierz M., Pierson S., Chouha N., Désaubry L., François JH., Berchem G., Paggetti J., Moussay E. Haematologica 103: e154-e157 (2018).

Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours. Yurugi H., Marini F., Weber C., David K., Zhao Q., Binder H., Désaubry L., Rajalingam K. Oncogene  36: 4778-4789 (2017).

Pro-differentiating effects of a synthetic flavagline on human teratocarcinomal cancer stem-like cells. Emhemmed F, Ali Azouaou S, Zhao Q, Appert-Collin A, Bennasroune A, Schini-Kerth VB, Muller CD, Désaubry L, Fuhrmann G. Cell Biol Toxicol. 33: 295–306 (2017).

Flavaglines ameliorate experimental colitis and protect against intestinal epithelial cell apoptosis and mitochondrial dysfunction. Han J., Zhao Q., Basmadjian C., Désaubry L., Theiss A.L. Inflamm. Bowel Dis. 22: 55-67 (2016).

Flavaglines stimulate transient receptor potential melastatin type 6 (TRPM6) channel activity. Blanchard MG., de Baaij J.H.F., Verkaart S.A.J., Lameris A.L., Basmadjian C., Zhao Q., Désaubry L., Bindels R.J.M., Hoenderop JG. Plos One,  10: e0119028 (2015).FL3, a synthetic flavagline and ligand of prohibitins, protects cardiomyocytes via STAT3 from doxorubicin toxicity. Qureshi R., Yildirim O.,Gasser A., Basmadjian C., Zhao Q., Wilmet J-P., Désaubry L., Nebigil C.G. Plos One. 10:  e0141826 (2015).

Assessment of flavaglines as potential chikungunya virus entry inhibitors. Wintachai P., Thuaud F., Basmadjian C., Ubol S., Désaubry L., Smith D.R. Microbiol Immuno. 59: 129–141 (2015).

Selective anticancer effects of a synthetic flavagline on human Oct-4 expressing cancer stem-like cells via a p38 MAPK-dependent caspase 3-dependent pathway. Emhemmed F., Azouaou S.A., Thuaud F., Schini-Kerth V., Désaubry L., Muller C., Fuhrmann G. Biochem. Pharmacol. 88: 185–196 (2014).

Flavaglines: potent anticancer drugs that target prohibitins and the eIF4 helicase. Basmadjian C, Thuaud F, Ribeiro N, Désaubry L. Future Med. Chem. 5: 2185-2197 (2013).

Reproduced from Future Medicinal Chemistry with permission of Future Science Ltd.

Prohibitin Ligands in Cell Death and Survival: Mode of Action and Therapeutic Potential. Thuaud F, Ribeiro N, Nebigil CG, Désaubry L. Chem Biol. 20:316–331 (2013).    Selected as a Top 25 hottest articles by ScienceDirect.

Flavaglines as Potent Anticancer and Cytoprotective Agents. Ribeiro N, Thuaud F, Bernard Y, Gaiddon C, Cresteil T, Hild A, Hirsch EC, Michel PP, Nebigil CG, Désaubry L. J. Med. Chem. 55: 10064–10073 (2012).

The Natural Anticancer Compounds Rocaglamides Inhibit the Raf-MEK-ERK Pathway by Targeting Prohibitin 1 and 2. Polier G, Neumann J, Thuaud F, Ribeiro N, Gelhaus C, Schmidt H, Giaisi M, Köhler R, Müller W, Proksch P, Leippe M, Janssen O, Désaubry L, Krammer P H, Li-Weber M. Chem Biol 19: 1093-1104 (2012).              Selected as a Top 25 hottest articles by ScienceDirect.

Recent advances in the biology and chemistry of the flavaglines. Ribeiro N., Thuaud F., Nebigil C., Désaubry L. Bioorg. Med. Chem. Lett. 20: 1857-64 (2012).

Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27. Bernard Y., Ribeiro N., Thuaud F., Türkeri G., Dirr R, Boulberdaa M., Nebigil C., Désaubry L. Plos One 6: e25302, (2011).

Novel Flavaglines Displaying Improved Cytotoxicity. Thuaud F., Ribeiro N., Gaiddon C., Cresteil T., Désaubry L. J. Med. Chem. 54 : 411-415 (2011).

Synthetic Analogue of Rocaglaol Displays a Potent and Selective Cytotoxicity in Cancer cells: Involvement of Apoptosis Inducing Factor and Caspase-12. Thuaud F., Bernard Y., Türkeri G., Dirr R., Aubert G., Cresteil T., Baguet A., Tomasetto C., Svitkin Y., Sonenberg N., Nebigil CG., Désaubry L. J.Med. Chem. 52: 5176-5187, (2009).

FL3, a synthetic flavagline and ligand of prohibitins, protects cardiomyocytes via STAT3 from doxorubicin toxicity. Qureshi R., Yildirim O.,Gasser A., Basmadjian C., Zhao Q., Wilmet J-P., Désaubry L., Nebigil C.G. Plos One.10:  e0141826 (2015).