Concept

Mixed inhibition

Related publications (15)

Antibody-peptide conjugates for targeted inhibition of cysteine proteases

We developed a rational approach to design peptide-based covalent inhibitors and coupled the inhibitors with antibodies for cell-specific delivery. We used this platform to generate antibody-peptide inhibitor conjugates (APICs) that target a family of prot ...

Nature Portfolio2024

Structural Basis of the Allosteric Inhibition of Human ABCG2 by Nanobodies

Henning Paul-Julius Stahlberg, Dongchun Ni

ABCG2 is an ATP-binding cassette transporter that exports a wide range of xenobiotic compounds and has been recognized as a contributing factor for multidrug resistance in cancer cells. Substrate and inhibitor interactions with ABCG2 have been extensively ...

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD2023

Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1(T315I) and BCR-ABL1(T315I-E255K)

Oliver Hantschel

Resistance remains the major clinical challenge for the therapy of Philadelphia chromosome-positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common "gatekeeper" mutation T315I ...

SPRINGER2021

Btk SH2-kinase interface is critical for allosteric kinase activation and its targeting inhibits B-cell neoplasms

Matteo Dal Peraro, Florence Pojer, Sandrine Madeleine Suzanne Georgeon, Maria Josefina Marcaida Lopez, Oliver Hantschel, Allan Joaquim Lamontanara, Tim Kükenshöner, Grégory La Sala, Daniel Pereira Duarte

Bruton's tyrosine kinase (Btk) is critical for B-cell maturation and activation. Btk loss-of-function mutations cause human X-linked agammaglobulinemia (XLA). In contrast, Btk signaling sustains growth of several B-cell neoplasms which may be treated with ...

NATURE PUBLISHING GROUP2020

Allosteric regulation and targeting of Bruton's tyrosine kinase (Btk) in B-cell lymphoma

Daniel Pereira Duarte

Bruton's tyrosine kinase (Btk) is a key component of BCR signaling required for B-cell maturation and activation. Loss-of-function mutations throughout the Btk protein cause human X-linked agammaglobulinemia (XLA), a heritable genetic disorder characterize ...

EPFL2020

Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states

Henning Paul-Julius Stahlberg

ABCG2 is a transporter protein of the ATP-binding-cassette (ABC) family that is expressed in the plasma membrane in cells of various tissues and tissue barriers, including the blood-brain, blood-testis and maternal-fetal barriers(1-4). Powered by ATP, it t ...

Springer Nature America, Inc2018

The evolution of multiple active site configurations in a designed enzyme

Ganna Gryn'ova, Dusan Petrovic

Developments in computational chemistry, bioinformatics, and laboratory evolution have facilitated the de novo design and catalytic optimization of enzymes. Besides creating useful catalysts, the generation and iterative improvement of designed enzymes can ...

NATURE PUBLISHING GROUP2018

Kinetics, Mechanics and Micro-structure of Bio-cemented Soils

Dimitrios Terzis

The quest for novel, performant materials and methods in the engineering practice is driven nowadays by the need to offer solutions to complex problems by coupling technical innovation with environmental responsibility. Such problems emerge in the geo-tech ...

EPFL2017

Computational Investigation of Intracellular Signalling Cascades

Siri Camee van Keulen

In order to adjust to changes in the environment, cells can communicate via signalling cascades. A common pathway for intercellular communication is the G-protein-coupled- receptor (GPCR) signal transduction cascade which is triggered by a (chemical or phy ...

EPFL2017

A Balance between Inhibitor Binding and Substrate Processing Confers Influenza Drug Resistance

Jeffrey David Jensen, Claudia Bank, Li Jiang

The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to qu ...

Academic Press Ltd- Elsevier Science Ltd2016

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