Browsing Structural Biology by author "Matthews, Thomas"
Now showing items 1-3 of 3
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A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms.
Jones, AM; Westwood, IM; Osborne, JD; Matthews, TP; Cheeseman, MD; et al. (NATURE PORTFOLIO, 2016-10-06)The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority ... -
Binding to an Unusual Inactive Kinase Conformation by Highly Selective Inhibitors of Inositol-Requiring Enzyme 1α Kinase-Endoribonuclease.
Colombano, G; Caldwell, JJ; Matthews, TP; Bhatia, C; Joshi, A; et al. (AMER CHEMICAL SOC, 2019-02-19)A series of imidazo[1,2- b]pyridazin-8-amine kinase inhibitors were discovered to allosterically inhibit the endoribonuclease function of the dual kinase-endoribonuclease inositol-requiring enzyme 1α (IRE1α), a key component ... -
Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).
Osborne, JD; Matthews, TP; McHardy, T; Proisy, N; Cheung, K-MJ; et al. (AMER CHEMICAL SOC, 2016-06-09)Multiparameter optimization of a series of 5-((4-aminopyridin-2-yl)amino)pyrazine-2-carbonitriles resulted in the identification of a potent and selective oral CHK1 preclinical development candidate with in vivo efficacy ...