PUBLICATIONS
Mehellou, Y.* Parkinson’s Disease: Are PINK1 Activators Inching Closer to the Clinic? ACS Med. Chem. Lett. 2023, DOI: 10.1021/acsmedchemlett.3c00070.
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Lambourne, O. A.; Bell, S.; Wilhelm, L. P.; Yarbrough, E. B.; Holly, G. G.; Russell, O. M.; Alghamdi, A. M.; Fdel, A. M.; Varricchio, C.; Lane, E. L.; Ganley, I. G.; Jones, A. T.; Goldberg, M. S.; Mehellou, Y.* PINK1-Dependent Mitophagy Inhibits Elevated Ubiquitin Phosphorylation Caused by Mitochondrial Damage. J. Med. Chem. 2023, 66, 11, 7645-7656. [link]
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Lambourne, O. A.; Bell, S.; Wilhelm, L. P.; Yarbrough, E. B.; Holly, G. G.; Russell, O. M.; Alghamdi, A.; Fdel, A. M.; Varricchio, C.; Lane, E. L.; Ganley, I. G.; Jones, A. T.; Goldberg, M. S.; Mehellou, Y.* Inhibition of Ubiquitin Phosphorylation by Nucleoside Analogues. ChemRxiv 2022, DOI: 10.26434/chemrxiv-2022-vcp3x. [link]
​Alanazi, A. S.; Miccoli, A.; Mehellou, Y.* Aryloxy Pivaloyloxymethyl Prodrugs as Nucleoside Monophosphate Prodrugs. J. Med. Chem. 2021, 64, 16703-16710. [link]
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Elvers, K. T.; Lipka-Lloyd, M.; Trueman, R. C.; Bax, B. D.; Mehellou, Y.* Structures of the Human SPAK and OSR1 Conserved C-Terminal (CCT) Domains. ChemBioChem 2022, 23, e202100441. [link]
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Qin, X.; Taher, T. E.; Ashby, E.; Sharif, M.; Willcox, B. E.; Mehellou, Y.* Generation of Stable Isopentenyl Monophosphate Aryloxy Triester Phosphoramidates as Activators of Vγ9Vδ2 T Cells. ChemMedChem 2021, 16, 2375-2380. [link]
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Mehellou, Y.;* Willcox, B. E.* A Two-Pronged Attack on Antibiotic-Resistant Microbes. Nature 2021, 589, 517-518. [link]
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Kadri, K.; Taher, T. E.; Xu, Q.; Sharif, M.; Ashby, E.; Bryan, R. T.; Willcox, B. E.; Mehellou, Y.* Aryloxy Diester Phosphonamidate Prodrugs of Phosphoantigens (ProPAgens) as Potent Activators of Vγ9/Vδ2 T-Cell Immune Responses. J. Med. Chem. 2020, 63, 11258-11270. [link]
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Elzwawi, A.; Grafton, G.; Barnes, N. M.; Mehellou, Y.* SPAK and OSR1 kinases bind and phosphorylate the β2-Adrenergic receptor. Biochem. Biophys. Res. Commun. 2020, 532, 88-93. [link]
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Miccoli, A.; Dhiani, B. A.; Thornton, P. J.; Lambourne, O. A.; James, E.; Kadri, H.; Mehellou, Y*. Aryloxy Triester Phosphoramidates as Phosphoserine Prodrugs: A Proof of Concept Study. ChemMedChem 2020, 15, 671-674. [link]
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Dhiani, B. A.; Mehellou, Y.* The Cul4-DDB1-WDR3/WDR6 Complex Binds SPAK and OSR1 Kinases in a Phosphorylation-Dependent Manner. ChemBioChem 2020, 21, 638-643. [link]
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AlAmri, M. A.; Jeeves, M.; Mehellou, Y.* Sequence Specific Assignment and Determination of OSR1 C-terminal Domain Structure by NMR. Biochem. Biophys. Res. Commun. 2019, 512, 338-343. [link] Paper summary here.
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Alanazi, A. S.; James, E.; Mehellou, Y.* The ProTide Prodrug Technology: Where Next? ACS Med. Chem. Lett. 2019, 10, 2-5. [link]
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Miccoli, A.; Dhiani, B. A.; Mehellou, Y.* Phosphotyrosine Prodrugs: Design, Synthesis and Anti-STAT3 Activity of ISS-610 Aryloxy Triester Phosphoramidate Prodrugs. MedChemComm 2019, 10, 200-208. [link] Paper summary here.
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Lambourne, O. A.; Mehellou, Y.* Chemical strategies for activating PINK1, a protein kinase mutated in Parkinson's disease. ChemBioChem 2018, 19, 2433-2437. [link]
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Mehellou, Y.*; AlAmri, M. A.; Dhiani, B. A.; Kadri, H. C-terminal phosphorylation of SPAK and OSR1 kinases promotes their binding and activation by the scaffolding protein MO25. Biochem. Biophys. Res. Commun. 2018, 503, 1868-1873. [link] Paper summary here.
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AlAmri, M. A.; Kadri, H.; Alderwick, L. J.; Jeeves, M.; Mehellou, Y*. The Photosensitizing Clinical Agent Verteporfin is an Inhibitor of SPAK and OSR1 Kinases. ChemBioChem 2018, 19, 2072-2080. [link] Paper summary here.
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Kadri, H.; Taher. T. E.; Xu, Q.; Bryan, R. T.; Willcox, B. E.; Mehellou, Y*. Aryloxy Triester Phosphonamidates of Phosphoantigens Exhibit Favorable Stability and Potent Activation of Vγ9/Vδ2 T-Cells. ChemRxiv 2018, DOI: 10.26434/chemrxiv.6755033.v1. [link]
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Kadri, H.; Lambourne, O. A.; Mehellou, Y*. Niclosamide, a drug with many (re)purposes. ChemMedChem. 2018, 13, 1088-1091. [link]
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Davey, M. S.; Malde, R.; Mykura, R. C.; Baker, A. T.; Taher, T. E.; Le Duff, C. S.; Willcox, B. E.; Mehellou, Y*. Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-Methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses. J. Med. Chem. 2018, 61, 2111-2117. [link] Paper summary here.
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Barini, E.; Miccoli, A.; Tinarelli, F.; Mulholland, K.; Kadri, H.; Khanim, K.; Stojanovski, L.; Read, K. D.; Burness, K.; Blow, J. J.; Mehellou, Y*.; Muqit, M. M. The anthelmintic drug niclosamide and its analogues activate the Parkinson’s disease associated kinase PINK1. ChemBioChem. 2018, 19, 425-429. [link] Paper summary here.
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AlAmri, M.A.; Kadri, H.; Dhiani, B.A.; Mahmood, S.; Elzwawi, A.; Mehellou, Y*. WNK-Signaling Inhibitors as Potential New Antihypertensive Drugs. ChemMedChem 2017, 12, 1677-1686. [link]
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Salim, M.; Knowles, T.J.; Baker, A.T.; Davey, M.S.; Jeeves, M.; Sridhar, P.; Wilkie, J.; Willcox, C.R.; Kadri, H.; Taher, T.E.; Vantourout, P.; Hayday, A.; Mehellou, Y.; Mohammed, F.; Willcox, B.E. BTN3A1 discriminates γδ T cell phosphoantigens from non-antigenic small molecules via a conformational sensor in its B30.2 domain. ACS Chem. Biol. 2017, 12, 2631-2643. [link]
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Mehellou, Y.*; Rattan, H. S.; Balzarini, J. The ProTide Prodrug Technology: From the Concept to the Clinic. J. Med. Chem. 2018, 61, 2211-2226. [Link] ​
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AlAmri, M. A.; Kadri, H.; Alderwick, L. J.; Simpkins, N. S.; Mehellou, Y*. Rafoxanide and Closantel inhibit SPAK and OSR1 kinases by binding to a highly conserved allosteric site on their C-terminal domains. ChemMedChem 2017, 12, 639-645. [link]
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Osgerby, L.; Lai, Y. C.; Thornton, P. J.; Amalfitano, J.; Le Duff, C. S.; Jabeen, I.; Kadri, H.; Miccoli, A.; Tucker, J. H. R.; Muqit, M. M. K.; Mehellou. Y*. Kinetin riboside and its ProTides activate the Parkinson’s disease associated PTEN-induced putative kinase 1 (PINK1) independent of mitochondrial depolarisation. J. Med. Chem. 2017, 60, 3518-3524. [link] Paper summary here.
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Kadri, H.; AlAmri, M. A.; Navratilova, I. H.; Alderwick, L. J.; Simpkins, N. S.; Mehellou, Y*. Towards the development of small molecule MO25-binders as potential indirect SPAK/OSR1 kinase inhibitors. ChemBioChem 2017, 18, 460-465. [link]​. This article featured on the Cover of ChemBioChem. [link] Paper summary here.
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Kedge, J. L.; Nguyen, H. V.; Khan, K.; Male, L.; Ismail, M. K.; Roberts, H. V.; Hodges, N. J.; Horswell, S. L.; Mehellou, Y.; Tucker, J. H. R. Organometallic Nucleoside Analogues: Effect of Hydroxyalkyl Linker Length on Cancer Cell Line Toxicity. Eur. J. Inorg. Chem. 2017, 466–476. [link]
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Thornton, P.J.; Kadri, H.; Miccoli, A.; Mehellou, Y*. Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates. J. Med. Chem. 2016, 59, 10400-10410. [link]
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Mehellou, Y*. The ProTides Boom. ChemMedChem 2016, 11, 1114-1116. [link]
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PATENT: International patent (PCT/GB2014/053794): ‘Ferrocenyl nucleosides as nucleoside analogues and uses thereof’. Inventors: Tucker, J. H. R.; Nguyen, H. V.; Hodges, N.; Mehellou, Y.; Tselepis, C. 2015. [link]
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Nguyen, H. V.; Sallustrau, A.; Balzarini, J.; Bedford, M. R.; Eden, J C.; Georgousi, N.; Hodges, N. J.; Kedge, J.; Mehellou, Y.; Tselepis, C.; Tucker, J. H. Organometallic nucleoside analogues with ferrocenyl linker groups: synthesis and cancer cell line studies. J. Med. Chem. 2014, 57, 5817-22. [link]
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Ohta, A.; Schumacher, F. R.; Mehellou, Y.; Johnson, C.; Knebel, A.; Macartney, T. J.; Wood, N. T.; Alessi, D. R.; Kurz, T. The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. Biochem. J. 2013, 451, 111-122. [link]
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Mehellou, Y*.; Alessi, D. R.; Macartney, T. J.; Szklarz, M.; Knapp, S., Elkins, J. M. Structural insights into the activation of MST3 by MO25. Biochem. Biophys. Res. Commun. 2013, 431, 604-609. [link]
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Chen, S.; Fahmi, N. E.; Nangreave, R. C.; Mehellou, Y.; Hecht, S. M. Synthesis of pdCpAs and transfer RNAs activated with thiothreonine and derivatives. Bioorg. Med. Chem. 2012, 20, 2679-2689. [link]
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Thastrup JO, Rafiqi FH, Vitari AC, Pozo-Guisado E, Deak M, Mehellou Y, Alessi DR. SPAK/OSR1 regulate NKCC1 and WNK activity: analysis of WNK isoform interactions and activation by T-loop trans-autophosphorylation. Biochem. J. 2012, 441, 325-337. [link]
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Filippi BM, de los Heros P, Mehellou Y, Navratilova I, Gourlay R, Deak M, Plater L, Toth R, Zeqiraj E, Alessi DR. MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases. EMBO J. 2011, 30, 1730-1741. [link]
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Mehellou Y*. Phosphoramidate prodrugs deliver with potency against hepatitis C virus. ChemMedChem. 2010, 5, 1841-1842. [link]
Mehellou Y, Valente R, Mottram H, Walsby E, Mills KI, Balzarini J, McGuigan C.Phosphoramidates of 2'-beta-D-arabinouridine (AraU) as phosphate prodrugs; design, synthesis, in vitro activity and metabolism. Bioorg. Med. Chem. 2010, 18, 2439-2446. [link]
Mehellou Y, Balzarini J, McGuigan C. The design, synthesis and antiviral evaluation of a series of 5-trimethylsilyl-1-beta-D-(arabinofuranosyl)uracil phosphoramidate ProTides. Antivir. Chem. Chemother. 2010, 20, 153-160. [link]
Mehellou Y*, De Clercq E. Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go? J. Med. Chem. 2010, 53(2), 521-538. [link]
Mehellou Y, Balzarini J, McGuigan C. Aryloxy phosphoramidate triesters: a technology for delivering monophosphorylated nucleosides and sugars into cells. ChemMedChem. 2009, 4, 1779-1791. [link]
Mehellou Y, Balzarini J, McGuigan C. An investigation into the anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U) and 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives. Org. Biomol. Chem. 2009, 7, 2548-2553. [link]
Mehellou Y, McGuigan C, Brancale A, Balzarini J. Design, synthesis, and anti-HIV activity of 2',3'-didehydro-2',3'-dideoxyuridine (d4U), 2',3'-dideoxyuridine (ddU) phosphoramidate 'ProTide' derivatives. Bioorg. Med. Chem. Lett. 2007, 17, 3666-3669. [link]