Accès ouvert
2026
article
OpenAlex
Ana Corrionero, Niall Prendiville, Tatiana Cazorla, M. Baena-Nuevo et autres
In cancer therapy, traditional approaches often overlook the dynamic nature of drug‐target interactions. We introduce kinetic fingerprints as a mechanistically informative tool to guide kinase inhibitor design and predict clinical performance. Profiling 172 compounds across multiple KIT conformations, including the oncogenic D816V …
es, de
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Accès ouvert
2026
preprint
OpenAlex
Bharath Srinivasan, Ana Corrionero, Marco Barone, Patricia Alfonso et autres
SUMMARY Protein–ligand interactions underpin biological regulation and drug action, with both binding affinity and binding kinetics shaping functional outcomes. By analysing kinetic data for 4,311 protein-small-molecule pairs, we find that when association occurs below the diffusion-controlled limit, the rates of ligand association …
gb, us, es
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Accès ouvert
2026
preprint
OpenAlex
Ana Corrionero, Niall Prendiville, Tatiana Cazorla, M. Baena-Nuevo et autres
Abstract In cancer therapy, traditional approaches often overlook the dynamic nature of drug-target interactions. We introduce kinetic fingerprints as a mechanistically informative tool to guide kinase inhibitor design and predict clinical performance. Profiling 172 compounds across multiple KIT conformations, including the oncogenic …
es, de
(code pays fourni par la source)
Accès ouvert
2025
article
OpenAlex
Ana Corrionero, Xiaohu Zhang, Patricia Alfonso, Patrick J. Morris et autres
Inhibitors of the Bruton's tyrosine kinase (BTK) are of broad utility in the treatment of multiple diseases including several B-cell malignancies via effective blockade of oncogenic B-cell receptor (BCR) signaling. BTK is a cytoplasmic tyrosine kinase which harbors a targetable cysteine residue …
us, in
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Accès ouvert
2025
article
OpenAlex
Yong Li, David Yin-wei Lin, Bharath Srinivasan, Marco Barone et autres
Optimization exercises strive toward increasing the efficacy and selectivity of small molecules toward the target of interest while simultaneously phasing out design elements that lead to off-target interactions. Given the nonequilibrium nature of biological systems, greater reliance should be placed on engineering …
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Accès ouvert
2025
article
OpenAlex
Sebastian Mandel, Thomas Hanke, Niall Prendiville, María Baena-Nuevo et autres
Selectivity for closely related isoforms of protein kinases is a major challenge in the design of drugs and chemical probes. Covalent targeting of unique cysteines is a potential strategy to achieve selectivity for highly conserved binding sites. Here, we used a pan-LIMK …
de, us, ch
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Accès ouvert
2025
preprint
OpenAlex
Sebastian Mandel, Thomas Hanke, Niall Prendiville, M. Baena-Nuevo et autres
Abstract Selectivity for closely related isoforms of protein kinases is a major challenge in the design of drugs and chemical probes. Covalent targeting of unique cysteines is a potential strategy to achieve selectivity for highly conserved binding sites. Here, we used a …
de
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Accès ouvert
2025
article
OpenAlex
Sebastian Mandel, Thomas Hanke, Sebastian Mathea, Deep Chatterjee et autres
High Resolution Image Download MS PowerPoint Slide Benzoxazepinones have been extensively studied as exclusively selective RIP kinase 1 inhibitors. This scaffold binds to an allosteric pocket created by an αC-out/DFG-out conformation. This inactive conformation results in a large expansion of the kinase …
de, us, jp
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Accès ouvert
2025
preprint
OpenAlex
Sebastian Mandel, Thomas Hanke, Sebastian Mathea, Deep Chatterjee et autres
Abstract Benzoxazepinones have been extensively studied as exclusively selective RIP kinase 1 inhibitors. This scaffold binds as a type-III inhibitor targeting the αC-out/DFG-out conformation. This inactive conformation results in a large expansion of the kinase back pocket, a conformation that has also …
de, us, jp
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Accès ouvert
2023
article
OpenAlex
Yi-Qian Li, William G. Lannigan, Shabnam Davoodi, Fereidoon Daryaee et autres
Bruton’s tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases, and several BTK inhibitors are already approved for use in humans. Heterobivalent BTK protein degraders are also in development, based on the premise that proteolysis targeting chimeras (PROTACs) …
us
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Accès ouvert
2023
article
OpenAlex
Mattias F. Lindberg, Emmanuel Deau, Jonas Arfwedson, Nicolas S. George et autres
Dual-specificity, tyrosine phosphorylation-regulated kinases (DYRKs) and cdc2-like kinases (CLKs) play a large variety of cellular functions and are involved in several diseases (cognitive disorders, diabetes, cancers, etc.). There is, thus, growing interest in pharmacological inhibitors as chemical probes and potential drug candidates. …
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Accès ouvert
2023
article
OpenAlex
Kaixuan Li, Mingqian Wang, Melike Akoglu, Alyssa C. Pollard et autres
Bruton’s tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases. To aid in the discovery and development of BTK inhibitors and improve clinical diagnoses, we have developed a positron emission tomography (PET) radiotracer based on a selective BTK …
us
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