Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?

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The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

Cysteine cathepsins are a family of proteases that are relevant therapeutic targets for the treatment of different cancers and other diseases. However, no clinically approved drugs for these proteins exist, as their systemic inhibition can induce deleterio ...

The dysregulated post-translational modification of proteins is an established hallmark of human disease. Through Zn2+-dependent hydrolysis of acyl-lysine modifications, histone deacetylases (HDACs) are key regulators of disease-implicated signaling pathwa ...

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

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Redox homeostasis is a key factor in maintaining cellular function and health. The main determinant of the intracellular redox potential is ubiquitous glutathione (GSH) together with its oxidized dimer (GSSG). Importantly, both redox equilibrium and GSH ho ...

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An unprecedent asymmetric catalytic benzilic amide rearrangement for the synthesis of α,α-disubstituted piperazinones is reported. The reaction proceeds via a domino [4+1] imidazolidination/formal 1,2-nitro- gen shift/1,2-aryl or alkyl migration sequence, ...

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to e ...

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Native reactive electrophile species (RES) such as 4-hydroxynonenal (HNE) act as cellular signals through covalent modification of kinetically-privileged electrophile sensor proteins. Research efforts in the field focus mainly on identifying these sensor p ...

Activin-A is a Transforming Growth Factor-B (TGFB)-related cytokine that regulates various biological processes including cell proliferation and differentiation through autocrine, paracrine or endocrine signaling. Activin-A expression is upregulated in mul ...

Glutathione (GSH) is the main determinant of intracellular redox potential and participates in multiple cellular signalling pathways. Achieving a detailed understanding of intracellular GSH homeostasis depends on the development of tools to map GSH compart ...

Reactive metabolites and related electrophilic drugs are among the most challenging small molecules to study. Conventional approaches to deconstruct the mode of action (MOA) of such molecules leverage bulk treatment of experimental specimens with an excess ...

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The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we ...

Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?

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Computational drug development for membrane protein targets

Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins

Slow-Binding and Covalent HDAC Inhibition: A New Paradigm?

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Antibody-peptide conjugates for targeted inhibition of cysteine proteases

HaloTag-Based Tools for Live-Cell Imaging and Elucidation of Organellar Redox Biology

The autism susceptibility kinase, TAOK2, phosphorylates eEF2 and modulates translation

Engineering hydrogel microenvironments for epithelial organoid culture

Optimised three-dimensional in vitro retinoblastoma models tailored for drug discovery and clinical translatability

Asymmetric Construction of α,α‐Disubstituted Piperazinones Enabled by Benzilic Amide Rearrangement

Artificial intelligence for natural product drug discovery

Unlocking Hidden Potential: Exploring the Complexities of Signaling in Immune Cell Activation to Optimize CAR Therapy

Towards Uncovering the Mechanisms of Electrophile Sensing and Signaling

Regulation and function of a hemicleaved Activin-A processing intermediate in melanoma

A locally activatable sensor for robust quantification of organellar glutathione

Monitoring On-Target Signaling Responses in Larval Zebrafish- Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites

Rational design of protein switches: applications in synthetic biology and cancer immunotherapy

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis