Browsing by author "Caldwell, John"
Now showing items 1-10 of 10
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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 ... -
Chemical approaches to targeted protein degradation through modulation of the ubiquitin-proteasome pathway.
Collins, I; Wang, H; Caldwell, JJ; Chopra, R (PORTLAND PRESS LTD, 2017-03-15)Manipulation of the ubiquitin-proteasome system to achieve targeted degradation of proteins within cells using chemical tools and drugs has the potential to transform pharmacological and therapeutic approaches in cancer ... -
Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766).
Chessum, NEA; Sharp, SY; Caldwell, JJ; Pasqua, AE; Wilding, B; et al. (AMER CHEMICAL SOC, 2018-02-08)Demonstrating intracellular protein target engagement is an essential step in the development and progression of new chemical probes and potential small molecule therapeutics. However, this can be particularly challenging ... -
Determination of Ligand-Binding Affinity (Kd) Using Transverse Relaxation Rate (R2) in the Ligand-Observed 1H NMR Experiment and Applications to Fragment-Based Drug Discovery.
Liu, M; Mirza, A; McAndrew, PC; Thapaliya, A; Pierrat, OA; et al. (AMER CHEMICAL SOC, 2023-08-10)High hit rates from initial ligand-observed NMR screening can make it challenging to prioritize which hits to follow up, especially in cases where there are no available crystal structures of these hits bound to the target ... -
Fragment growing to retain or alter the selectivity of anchored kinase hinge-binding fragments
Allen, CE; Welford, AJ; Matthews, TP; Caldwell, JJ; Collins, I (ROYAL SOC CHEMISTRY, 2014-01-01)<p>The selectivity patterns of kinase hinge-binding fragments can be retained during fragment growing, suggesting a new way to control poly-pharmacology.</p> -
iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells.
Bouguenina, H; Nicolaou, S; Le Bihan, Y-V; Bowling, EA; Calderon, C; et al. (CELL PRESS, 2023-07-21)To address the limitation associated with degron based systems, we have developed iTAG, a synthetic tag based on IMiDs/CELMoDs mechanism of action that improves and addresses the limitations of both PROTAC and previous ... -
Molecular mechanisms of human IRE1 activation through dimerization and ligand binding.
Joshi, A; Newbatt, Y; McAndrew, PC; Stubbs, M; Burke, R; et al. (IMPACT JOURNALS LLC, 2015-05-30)IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although ... -
SimPLIT: Simplified Sample Preparation for Large-Scale Isobaric Tagging Proteomics.
Sialana, FJ; Roumeliotis, TI; Bouguenina, H; Chan Wah Hak, L; Wang, H; et al. (AMER CHEMICAL SOC, 2022-08-05)Large scale proteomic profiling of cell lines can reveal molecular signatures attributed to variable genotypes or induced perturbations, enabling proteogenomic associations and elucidation of pharmacological mechanisms of ... -
Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library.
Welford, AJ; Caldwell, JJ; Liu, M; Richards, M; Brown, N; et al. (WILEY-V C H VERLAG GMBH, 2016-04-11)The 2,11-cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran-based compounds designed to augment a typical ... -
Synthesis of a Ribose-Incorporating Medium Ring Scaffold via a Challenging Ring-Closing Metathesis Reaction.
Rankin, SS; Caldwell, JJ; Cronin, NB; van Montfort, RLM; Collins, I (WILEY-V C H VERLAG GMBH, 2016-09-01)A practical synthesis of a novel oxabicyclo[6.2.1]undecenetriol useful as a medicinal chemistry scaffold has been developed starting from l-ribose. The sequence involves an oxidation/Grignard addition sequence and a ...