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Concept

Drug development

Publications associées (30)

Deconvolution of ex-vivo drug screening data and bulk tissue expression predicts the abundance and viability of cancer cell subpopulations

Alexandre Coudray

Ex-vivo drug sensitivity screening (DSS) allows the prediction of cancer treatment effectiveness in a personalized fashion. However, it only provides a readout on mixtures of cells, potentially occulting important information on clinically relevant cell su ...

EPFL2023

Cyclic Peptides for Drug Development

Christian Heinis, Alexander Lund Nielsen, Xinjian Ji

Cyclic peptides are fascinating molecules abundantly found in nature and exploited as molecular format for drug development as well as other applications, ranging from research tools to food additives. Advances in peptide technologies made over many years ...

Wiley-VCH Verlag GmbH2024

Methods for high-throughput synthesis and screening of peptide libraries

Zsolt Bognár

Macrocycles provide an attractive modality for drug development but the identification of ligands to targets of interest is hindered by the lack of large macrocyclic compound libraries for high-throughput screening. A strategy to efficiently synthesize lar ...

EPFL2024

Computational drug development for membrane protein targets

Pierre Vogel, Henning Paul-Julius Stahlberg, Shuguang Yuan, Dongchun Ni, Babatunde Edukpe Ekundayo

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 ...

2024

Augmented Memory: Sample-Efficient Generative Molecular Design with Reinforcement Learning

Philippe Schwaller, Jeff Guo

Sample efficiency is a fundamental challenge in de novo molecular design. Ideally, molecular generative models should learn to satisfy a desired objective under minimal calls to oracles (computational property predictors). This problem becomes more apparen ...

Amer Chemical Soc2024

Large Libraries of Structurally Diverse Macrocycles Suitable for Membrane Permeation

Christian Heinis, Alessandro Angelini, Alexander Lund Nielsen, Mischa Schüttel, Manuel Leonardo Merz, Xinjian Ji, Anne Sofie Luise Zarda, Ganesh Kumar Mothukuri, Zsolt Bognár, Edward Jeffrey Will

Macrocycles offer an attractive format for drug development due to their good binding properties and potential to cross cell membranes. To efficiently identify macrocyclic ligands for new targets, methods for the synthesis and screening of large combinator ...

Wiley-VCH Verlag GmbH2024

Antibody-peptide conjugates for targeted inhibition of cysteine proteases

Elisa Oricchio

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

Machine learning-aided generative molecular design

Philippe Schwaller, Jeff Guo

Machine learning has provided a means to accelerate early-stage drug discovery by combining molecule generation and filtering steps in a single architecture that leverages the experience and design preferences of medicinal chemists. However, designing mach ...

Nature Portfolio2024

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

Irina Sinenko

Retinoblastoma, while relatively rare, stands as the most prevalent intraocular cancer. In Switzerland, the survival rate approaches 100%, but it drops to less than 50% in low-income countries. The current treatment options for retinoblastoma rely on a lim ...

EPFL2023

Improved antibody pharmacokinetics by disruption of contiguous positive surface potential and charge reduction using alternate human framework

Andrea Pfeifer, Tariq Afroz, Florence Gauye, Monisha Ratnam

Optimal pharmacokinetic (PK) properties of therapeutic monoclonal antibodies (mAbs) are essential to achieve the desired pharmacological benefits in patients. To accomplish this, we followed an approach comprising structure-based mAb charge engineering in ...

TAYLOR & FRANCIS INC2023

Label-free plasmonic microarray for multiplexed analysis of cells and tumor organoids

Yen-Cheng Liu

Investigating the dynamic activities of protein expression and signaling in living organisms is a crucial focus of intense research aimed at elucidating the processes that underlie disease progression and improving treatments and drug development. Resolvin ...

EPFL2023

Advancing first principle-based molecular dynamics of biological systems with machine learning

François Louis Mouvet

Molecular dynamics (MD) simulations have emerged as a transformative approach to analyse molecular systems at the atomic level, offering valuable insights into complex biological processes. Many biological phenomena can only accurately be described by inco ...

EPFL2023

Bioengineering human mini-intestines with in vivo-like complexity and function

Olga Mitrofanova

Biological research heavily relies on the use of animal models, which has made it difficult to answer specific questions about human biology and disease. However, with the advent of human organoids - miniature versions of tissues generated in 3D human stem ...

EPFL2023

Rational combination platform trial design for children and young adults with Diffuse Midline Glioma: a report from PNOC

Sebastian Martin Waszak

Diffuse midline glioma (DMG) is a devastating pediatric brain tumor unresponsive to hundreds of clinical trials. Approximately 80% of DMGs harbor H3K27M oncohistones, which reprogram the epigenome to increase the metabolic profile of the tumor cells. We ha ...

2023

A guide to preclinical evaluation of hydrogel-based devices for treatment of cartilage lesions

Dominique Pioletti, Peyman Karami, Yanheng Guo, Theofanis Stampoultzis

The drive to develop cartilage implants for the treatment of major defects in the musculoskeletal sys-tem has resulted in a major research thrust towards developing biomaterial devices for cartilage repair. Investigational devices for the restoration of ar ...

ELSEVIER SCI LTD2023

Organoids as tools for fundamental discovery and translation-A Keystone Symposia report

Matthias Lütolf

Complex three-dimensional in vitro organ-like models, or organoids, offer a unique biological tool with distinct advantages over two-dimensional cell culture systems, which can be too simplistic, and animal models, which can be too complex and may fail to ...

WILEY2022

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

Po-Jen Tseng

The goal of retinoblastoma (RB) treatment is to save the child's life, eyes and functional vision, with that order of priority. The management of RB is complex and involves strategically chosen methods of surgical enucleation, external beam radiotherapy, i ...

EPFL2022

Examining African contributions to global health: Reflections on knowledge circulation and innovation

Jérôme Chenal, Vitor Pessoa Colombo, Jürg Utzinger, Akuto Akpedze Konou, Julia Tischler

This article unites different disciplinary debates on ‘southern innovation’, ‘theory from the South’, and ‘decolonisation of knowledge’ in order to discuss existing understandings around the role of Africa in the production of health-related knowledge, pub ...

2022

Cyclative Release Strategy to Obtain Pure Cyclic Peptides Directly from the Solid Phase

Christian Heinis, Manuel Leonardo Merz, Sevan Mleh Habeshian

The synthesis of large numbers of cyclic peptides-required, for example, in screens for drug development-is currently limited by the need of chromatographic purification of individual peptides. Herein, we have developed a strategy in which cyclic peptides ...

2022

Balancing NAD(+) deficits with nicotinamide riboside: therapeutic possibilities and limitations

Carlos Canto Alvarez

Alterations in cellular nicotinamide adenine dinucleotide (NAD(+)) levels have been observed in multiple lifestyle and age-related medical conditions. This has led to the hypothesis that dietary supplementation with NAD(+) precursors, or vitamin B3s, could ...

SPRINGER BASEL AG2022