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2. Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor

Author

Szlavik, Zoltan, primary, Csekei, Marton, additional, Paczal, Attila, additional, Szabo, Zoltan B., additional, Sipos, Szabolcs, additional, Radics, Gabor, additional, Proszenyak, Agnes, additional, Balint, Balazs, additional, Murray, James, additional, Davidson, James, additional, Chen, Ijen, additional, Dokurno, Pawel, additional, Surgenor, Allan E, additional, Daniels, Zoe Marie, additional, Hubbard, Roderick E., additional, Le Toumelin-Braizat, Gaëtane, additional, Claperon, Audrey, additional, Lysiak-Auvity, Gaëlle, additional, Girard, Anne-Marie, additional, Bruno, Alain, additional, Chanrion, Maia, additional, Colland, Frédéric, additional, Maragno, Ana-Leticia, additional, Demarles, Didier, additional, Geneste, Olivier, additional, and Kotschy, Andras, additional

Published
2020
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3. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

Author

Kotschy, Andrs, Szlavik, Zoltn, Murray, James, Davidson, James, Maragno, Ana Leticia, Le Toumelin-Braizat, Gatane, Chanrion, Maa, Kelly, Gemma L., Gong, Jia-Nan, Moujalled, Donia M., Bruno, Alain, Csekei, Mrton, Paczal, Attila, Szabo, Zoltn B., Sipos, Szabolcs, Radics, Gbor, Proszenyak, Agnes, Balint, Balzs, Ondi, Levente, Blasko, Gbor, Robertson, Alan, Surgenor, Allan, Dokurno, Pawel, Chen, Ijen, Matassova, Natalia, Smith, Julia, Pedder, Christopher, Graham, Christopher, Studeny, Aurlie, Lysiak-Auvity, Galle, Girard, Anne-Marie, Grav, Fabienne, Segal, David, Riffkin, Chris D., Pomilio, Giovanna, Galbraith, Laura C. A., Aubrey, Brandon J., Brennan, Margs S., Herold, Marco J., Chang, Catherine, Guasconi, Ghislaine, Cauquil, Nicolas, Melchiore, Fabien, Guigal-Stephan, Nolwen, Lockhart, Brian, Colland, Frdric, Hickman, John A., Roberts, Andrew W., Huang, David C. S., Wei, Andrew H., Strasser, Andreas, Lessene, Guillaume, and Geneste, Olivier

Subjects
Metastasis -- Observations, Apoptosis -- Health aspects, Myelocytic leukemia -- Physiological aspects, Nonlymphoid leukemia -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Avoidance of apoptosis is critical for the development and sustained growth of tumours. The pro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the development of small molecules targeting this protein that are amenable for clinical testing has been challenging. Here we describe S63845, a small molecule that specifically binds with high affinity to the BH3-binding groove of MCL1. Our mechanistic studies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma, leukaemia and lymphoma cells, by activating the BAX/BAK-dependent mitochondrial apoptotic pathway. In vivo, S63845 shows potent anti-tumour activity with an acceptable safety margin as a single agent in several cancers. Moreover, MCL1 inhibition, either alone or in combination with other anti-cancer drugs, proved effective against several solid cancer-derived cell lines. These results point towards MCL1 as a target for the treatment of a wide range of tumours., Author(s): Andrs Kotschy [1]; Zoltn Szlavik [1]; James Murray [2]; James Davidson [2]; Ana Leticia Maragno [3]; Gatane Le Toumelin-Braizat [3]; Maa Chanrion [3]; Gemma L. Kelly [4, 5]; Jia-Nan [...]

Published
2016
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5. Abstract 4482: S64315 (MIK665) is a potent and selective Mcl1 inhibitor with strong antitumor activity across a diverse range of hematologic tumor models

Author

Maragno, Ana Leticia, primary, Mistry, Prakash, additional, Kotschy, András, additional, Szlavik, Zoltán, additional, Murray, James, additional, Davidson, James, additional, Toumelin-Braizat, Gaëtane Le, additional, Chanrion, Maïa, additional, Bruno, Alain, additional, Claperon, Audrey, additional, Maacke, Heiko, additional, Morris, Erick, additional, Wang, Youzhen, additional, Derreal, Alix, additional, Csekei, Márton, additional, Paczal, Attila, additional, Szabo, Zoltán, additional, Sipos, Szabolcs, additional, Proszenyak, Agnes, additional, Balint, Balázs, additional, Surgenor, Allan, additional, Dokurno, Pawel, additional, Matassova, Natalia, additional, Chen, Ijen, additional, Lysiak-Auvity, Gaëlle, additional, Girard, Anne-Marie, additional, Grave, Fabienne, additional, Colland, Frédéric, additional, Halilovic, Ensar, additional, and Geneste, Olivier, additional

Published
2019
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6. Crystal structure of the MBP-MCL1 complex with highly selective and potent inhibitor of MCL1

Author

Dokurno, P., primary, Kotschy, A., additional, Szlavik, Z., additional, Murray, J., additional, Davidson, J., additional, Csekei, M., additional, Paczal, A., additional, Szabo, Z., additional, Sipos, S., additional, Radics, G., additional, Proszenyak, A., additional, Balint, B., additional, Ondi, L., additional, Blasko, G., additional, Robertson, A., additional, Surgenor, A., additional, Chen, I., additional, Matassova, N., additional, Smith, J., additional, Pedder, C., additional, Graham, C., additional, and Geneste, O., additional

Published
2016
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12. LETTERS.

Author

Castaldo, Tony, Mullen, Anne, Bowyer, Adrian, Haller, Ben, Quinn, Tamara, Wartnaby, Charles, Harrison, Peter, Taylor, Mike, Edge, Sam, McDonald, Iain, Proszenyak, Helen, and Glover, Bryn

Subjects
DAIRY products in human nutrition, ELECTRONIC cigarettes, BLOOD donors
Abstract

Several letters to the editor are presented in response to articles in previous issues including "Gone Off" by Linda Geddes from July 25, 2015, an article on electronic cigarettes from May 30, 2015, and an article regarding blood donations in Great Britain from July 4, 2015.

Published
2015
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