The present invention provides compounds, compositions thereof, and methods of using the same for the modulation of STING, and the treatment of STING-mediated disorders.
-
Paragraph 00760
(2020/07/14)
Benzimidazole inhibitors of the protein kinase CHK2: Clarification of the binding mode by flexible side chain docking and protein-ligand crystallography
Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR. Unconstrained rigid docking o
Matijssen, Cornelis,Silva-Santisteban, M. Cris,Westwood, Isaac M.,Siddique, Samerene,Choi, Vanessa,Sheldrake, Peter,Van Montfort, Rob L.M.,Blagg, Julian
supporting information
p. 6630 - 6639
(2013/01/15)
Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles
The discovery of a series of novel, potent, and highly selective inhibitors of the DNA damage control kinase chk2 is disclosed. Here we report the first SAR study around inhibitors of this kinase. High-throughput screening of purified human chk2 led to the identification of a novel series of 2-arylbenzimidazole inhibitors of the kinase. Optimization was facilitated using homology models of chk2 and docking of inhibitors, leading to the highly potent 2-arylbenz-imidazole 2h (IC50 15 nM). Compound 2h is an ATP-competitive inhibitor of chk2 that dose dependency protects human CD4 + and CD8+ T-cells from apoptosis due to ionizing radiation. This work suggests that a selective small molecule inhibitor of chk2 could be a useful adjuvant to radiotherapy, increasing the therapeutic window of such treatment.
Arienti, Kristen L.,Brunmark, Anders,Axe, Frank U.,McClure, Kelly,Lee, Alice,Blevitt, Jon,Neff, Danielle K.,Huang, Liming,Crawford, Shelby,Pandit, Chennagiri R.,Karlsson, Lars,Breitenbucher, J. Guy
p. 1873 - 1885
(2007/10/03)
More Articles about upstream products of 41263-65-4