A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

Autor: Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond, Su Chu, Alan R. Healy, Gergana Popova, Andrés Pastor Fernández, Tanzina Mollick, Suhas Darekar, Saikiran K. Sedimbi, Marta Nekulova, Marijke C. C. Sachweh, Johanna Campbell, Maureen Higgins, Chloe Tuck, Mihaela Popa, Mireia Mayoral Safont, Pascal Gelebart, Zinayida Fandalyuk, Alastair M. Thompson, Richard Svensson, Anna-Lena Gustavsson, Lars Johansson, Katarina Färnegårdh, Ulrika Yngve, Aljona Saleh, Martin Haraldsson, Agathe C. A. D’Hollander, Marcela Franco, Yan Zhao, Maria Håkansson, Björn Walse, Karin Larsson, Emma M. Peat, Vicent Pelechano, John Lunec, Borivoj Vojtesek, Mar Carmena, William C. Earnshaw, Anna R. McCarthy, Nicholas J. Westwood, Marie Arsenian-Henriksson, David P. Lane, Ravi Bhatia, Emmet McCormack, Sonia Laín

Publikováno v: Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018)

Abstract The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We

Externí odkaz: https://doaj.org/article/c70bab1df6ec4076bb2c93aa455abeeb

Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability

Autor: Gergana, Popova, Marcus J G W, Ladds, Lars, Johansson, Aljona, Saleh, Johanna, Larsson, Lars, Sandberg, Sara Häggblad, Sahlberg, Weixing, Qian, Hjalmar, Gullberg, Neeraj, Garg, Anna-Lena, Gustavsson, Martin, Haraldsson, David, Lane, Ulrika, Yngve, Sonia, Lain

Publikováno v: Journal of medicinal chemistry. 63(8)

Human dihydroorotate dehydrogenase (DHODH), an enzyme in the de novo pyrimidine synthesis pathway, is a target for the treatment of rheumatoid arthritis and multiple sclerosis and is re-emerging as an attractive target for cancer therapy. Here we des

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::730cacbe2fb4d2d6dbf3f019a39b96f0
https://pubmed.ncbi.nlm.nih.gov/32212728

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

Autor: Karin Larsson, Tanzina Mollick, Richard Svensson, Mireia Mayoral Safont, Emma M. Peat, Yan Zhao, Anna Lena Gustavsson, Chloe Tuck, David P. Lane, Gergana Popova, Anna R. McCarthy, Katarina Färnegårdh, Maureen Higgins, John Lunec, Ulrika Yngve, Marcus J.G.W. Ladds, Andrés Pastor Fernández, Nicholas J. Westwood, Emmet McCormack, Alan R. Healy, Ingeborg M.M. van Leeuwen, Suhas Darekar, Catherine J. Drummond, Martin Haraldsson, Pascal Gelebart, Mihaela Popa, Marijke C.C. Sachweh, Lars Johansson, Sonia Lain, Ravi Bhatia, Zinayida Fandalyuk, Vicent Pelechano, Agathe C.A. D'Hollander, Borivoj Vojtesek, Su Chu, Mar Carmena, William C. Earnshaw, Alastair M. Thompson, Saikiran K. Sedimbi, Marta Nekulova, Maria Håkansson, Aljona Saleh, Marie Arsenian-Henriksson, Johanna Campbell, Marcela Franco, Björn Walse

Publikováno v: Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018)
Nature Communications
Ladds, M J G W, van Leeuwen, I M M, Drummond, C J, Chu, S, Healy, A R, Popova, G, Pastor Fernández, A, Mollick, T, Darekar, S, Sedimbi, S K, Nekulova, M, Sachweh, M C C, Campbell, J, Higgins, M, Tuck, C, Popa, M, Safont, M M, Gelebart, P, Fandalyuk, Z, Thompson, A M, Svensson, R, Gustavsson, A-L, Johansson, L, Färnegårdh, K, Yngve, U, Saleh, A, Haraldsson, M, D'Hollander, A C A, Franco, M, Zhao, Y, Håkansson, M, Walse, B, Larsson, K, Peat, E M, Pelechano, V, Lunec, J, Vojtesek, B, Carmena, M, Earnshaw, W C, McCarthy, A R, Westwood, N J, Arsenian-Henriksson, M, Lane, D P, Bhatia, R, McCormack, E & Laín, S 2018, ' A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage ', Nature Communications, vol. 9, no. 1, 1107 (2018) . https://doi.org/10.1038/s41467-018-03441-3

ML, CD, IvL, GP, TM, SD, MS, APF, CT, DL, MAH, KL and SL: project grants from the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. MHi and JC: Cancer Research UK (C8/A6613). MC, EP and WE: Wellcome Tru

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5dd2c01d2aabbdecaf13d8d9d9ac446c
http://link.springer.com/article/10.1038/s41467-018-03441-3

Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

Autor: Mireia Mayoral Safont, Björn Walse, Katarina Färnegårdh, Lars Johansson, Marie Arsenian-Henriksson, Pascal Gelebart, Alan R. Healy, Marijke C.C. Sachweh, Johanna Campbell, Marcela Franco, Marta Nekulova, Richard Svensson, Maria Håkansson, Tanzina Mollick, Borivoj Vojtesek, Emmet McCormack, Anna Lena Gustavsson, Yan Zhao, Mar Carmena, John Lunec, Aljona Saleh, Sonia Lain, Ravi Bhatia, Anna R. McCarthy, Marcus J.G.W. Ladds, Saikiran K. Sedimbi, Suhas Darekar, Catherine J. Drummond, Zinayida Fandalyuk, Agathe C.A. D'Hollander, Vicent Pelechano, Ulrika Yngve, Su Chu, Karin Larsson, Alastair M. Thompson, Ingeborg M.M. van Leeuwen, Chloe Tuck, Martin Haraldsson, Mihaela Popa, Emma M. Peat, Gergana Popova, Maureen Higgins, Andrés Pastor Fernández, Nicholas J. Westwood, William C. Earnshaw, David P. Lane

Publikováno v: Nature Communications
Nature Communications, Vol 9, Iss 1, Pp 1-2 (2018)

The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidat

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d805f7ca635514dcfc03b4f3e80cf7d7
https://doi.org/10.1038/s41467-018-04198-5

3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel NaV1.7 with Efficacy in Rat Pain Models

Autor: Tjerk Bueters, Gabor Csjernyik, Nilsson Linda I, Per-Eric Lund, Yevgeni Besidski, Istvan Macsari, Per I. Arvidsson, Ulrika Yngve, Sandra Oerther, Kristofer Åhlin, Lars Sandberg, Karin Hygge Blakeman, Lei Luo, Anders B. Eriksson, Elisabet Venyike

Publikováno v: Journal of Medicinal Chemistry. 55:6866-6880

The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious advers

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8dd6fc194f3a561bd685e038690c2a01
https://doi.org/10.1021/jm300623u