This title appears in the Scientific Report :
2017
Please use the identifier:
http://dx.doi.org/10.1016/j.bmcl.2017.04.026 in citations.
Sulfoximines as ATR inhibitors: Analogs of VE-821
Sulfoximines as ATR inhibitors: Analogs of VE-821
The ATM- and Rad3-related (ATR) kinases play a key role in DNA repair processes and thus ATR is an attractive target for cancer therapy. Here we designed and synthesized sulfilimidoyl- and sulfoximidoyl-substituted analogs of the sulfone VE-821, a reported ATR inhibitor. The properties of these anal...
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Personal Name(s): | Hendriks, Christine M. M. |
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Hartkamp, Jörg / Wiezorek, Stefan / Steinkamp, Anne-Dorothee / Rossetti, Giulia / Lüscher, Bernhard / Bolm, Carsten (Corresponding author) | |
Contributing Institute: |
Computational Biomedicine; IAS-5 Computational Biomedicine; INM-9 Jülich Supercomputing Center; JSC |
Published in: | Bioorganic & medicinal chemistry letters, 27 (2017) 12, S. 2659 - 2662 |
Imprint: |
Amsterdam [u.a.]
Elsevier Science
2017
|
DOI: |
10.1016/j.bmcl.2017.04.026 |
Document Type: |
Journal Article |
Research Program: |
Computational Science and Mathematical Methods (Dys-)function and Plasticity |
Publikationsportal JuSER |
The ATM- and Rad3-related (ATR) kinases play a key role in DNA repair processes and thus ATR is an attractive target for cancer therapy. Here we designed and synthesized sulfilimidoyl- and sulfoximidoyl-substituted analogs of the sulfone VE-821, a reported ATR inhibitor. The properties of these analogs have been investigated by calculating physicochemical parameters and studying their potential to specifically inhibit ATR in cells. Prolonged inhibition of ATR by the analogs in a Burkitt lymphoma cell line resulted in enhanced DNA damage and a substantial amount of apoptosis. Together our findings suggest that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. |