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Your search keyword '"Pawel Dokurno"' showing total 4 results
Start Over Author "Pawel Dokurno" Publisher american chemical society
4 results on '"Pawel Dokurno"'

1. The Effect of Core Replacement on S64315, a Selective MCL‑1 Inhibitor, and Its Analogues

Author

Szabolcs Sipos, Balázs Bálint, Zoltán B. Szabó, Levente Ondi, Márton Csékei, Zoltán Szlávik, Ágnes Proszenyák, James B. Murray, James Davidson, Ijen Chen, Pawel Dokurno, Allan E. Surgenor, Christopher Pedder, Roderick E. Hubbard, Ana-Leticia Maragno, Maia Chanrion, Frederic Colland, Olivier Geneste, and András Kotschy

Subjects
Chemistry, QD1-999
Published
2021
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2. Establishing Drug Discovery and Identification of Hit Series for the Anti-apoptotic Proteins, Bcl‑2 and Mcl‑1

Author

James B. Murray, James Davidson, Ijen Chen, Ben Davis, Pawel Dokurno, Christopher J. Graham, Richard Harris, Allan Jordan, Natalia Matassova, Christopher Pedder, Stuart Ray, Stephen D. Roughley, Julia Smith, Claire Walmsley, Yikang Wang, Neil Whitehead, Douglas S. Williamson, Patrick Casara, Thierry Le Diguarher, John Hickman, Jerome Stark, András Kotschy, Olivier Geneste, and Roderick E. Hubbard

Subjects
Chemistry, QD1-999
Published
2019
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3. The Effect of Core Replacement on S64315, a Selective MCL‑1 Inhibitor, and Its Analogues

Author

I-Jen Chen, Proszenyák Ágnes, Zoltán B. Szabó, Levente Ondi, Csékei Márton, Olivier Geneste, Szabolcs Sipos, Allan E. Surgenor, Frédéric Colland, C. Pedder, Maïa Chanrion, Balázs Bálint, Ana-Leticia Maragno, Roderick E. Hubbard, Szlávik Zoltán, Pawel Dokurno, András Kotschy, James B. Murray, and James R. Davidson

Subjects
Cellular activity, Pyrimidine, Stereochemistry, General Chemical Engineering, General Chemistry, Article, chemistry.chemical_compound, Chemistry, chemistry, In vivo, Epimer, Tumor growth, Swap (computer programming), QD1-999
Abstract

Following the identification of thieno[2,3-d]pyrimidine-based selective and potent inhibitors of MCL-1, we explored the effect of core swapping at different levels of advancement. During hit-to-lead optimization, X-ray-guided S-N replacement in the core provided a new vector, whose exploration led to the opening of the so-called deep-S2 pocket of MCL-1. Unfortunately, the occupation of this region led to a plateau in affinity and had to be abandoned. As the project approached selection of a clinical candidate, a series of core swap analogues were also prepared. The affinity and cellular activity of these compounds showed a significant dependence on the core structure. In certain cases, we also observed an increased and accelerated epimerization of the atropoisomers. The most potent core replacement analogues showed considerable in vivo PD response. One compound was progressed into efficacy studies and inhibited tumor growth.

Published
2021

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