Publications related to Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors

Optimality principles for the analysis of biological processes across scales: From enzyme kinetics to microbiome dynamics

Microorganisms are essential for life on Earth, performing key roles in numerous biological processes. Their influence extends across a wide spectrum, from human health and ecological balance to advancements in biotechnology and industrial applications. Th ...

EPFL2024

A First-in-Human Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics, and Neutralization Profile of Two Investigational Long-Acting Anti-SARS-CoV-2 Monoclonal Antibodies

Didier Trono, Norman Lionel Moullan

Introduction: COVID-19 remains a significant risk for the immunocompromised given their lower responsiveness to vaccination or infection. Therefore, passive immunity through long-acting monoclonal antibodies (mAbs) offers a needed approach for pre-exposure ...

2024

Modeling tumor size dynamics based on real-world electronic health records and image data in advanced melanoma patients receiving immunotherapy

Olivier Michielin, Monia Guidi, Alexandre Wicky, Nadia Terranova, Daniel Abler, Federico Amato

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy but only a fraction of patients benefits from this therapy. Model-informed drug development can be used to assess prognostic and predictive clinical factors or biomark ...

2023

Elucidating and modulating regulatory pathways so as to reprogram the immunosuppressive tumor microenvironment for therapeutic benefit

Agnieszka Alicja Chryplewicz

Glioblastoma (GBM) is the most frequent and highly malignant form of brain cancer. New therapeutic regimens are urgently needed as GBM patients present with a minimal response to currently-approved therapies. The goal of this project is to identify new the ...

EPFL2023

Targeting the Progesterone Receptor in Breast Cancer: Mind the Short Form!

Cathrin Brisken, Carlos Henrique Venturi Ronchi

The presurgical window of opportunity trial (WOT) MIPRA provides evidence that neoadjuvant treatment with the prog-esterone receptor (PR) antagonist mifepristone (RU486) may benefit patients with estrogen receptor-positive (ER+) breast cancer characterized ...

AMER ASSOC CANCER RESEARCH2023

Model-based scale-up of a continuously operated consolidated bioprocess based on a microbial consortium for the production of ethanol

David Beat Dempfle

This work demonstrated that consolidated bioprocessing is a promising concept for conversion of lignocellulose to ethanol at industrial scale. CBP offers great cost saving potential, is feasible to be operated continuously and may be scaled up due to exten ...

EPFL2022

Investigation of Carboxylic Acid Isosteres and Prodrugs for Inhibition of the Human SIRT5 Lysine Deacylase Enzyme

Alexander Lund Nielsen

Sirtuin 5 (SIRT5) is a protein lysine deacylase enzyme that regulates diverse biology by hydrolyzing epsilon-N-carboxyacyllysine posttranslational modifications in the cell. Inhibition of SIRT5 has been linked to potential treatment of several cancers but ...

Wiley-VCH Verlag GmbH2022

Role of the cystathionine beta-synthase / H2S pathway in the development of cellular metabolic dysfunction and pseudohypoxia in down syndrome

Theodora Panagaki

Background: Overexpression of the transsulfuration enzyme cystathionine-beta-synthase (CBS), and overproduction of its product, hydrogen sulfide (H2S) are recognized as potential pathogenetic factors in Down syndrome (DS). The purpose of the study was to d ...

ELSEVIER2022

Assessing and enhancing foldability in designed proteins

Bruno Emanuel Ferreira De Sousa Correia, Che Yang, Stéphane Rosset

Recent advances in protein-design methodology have led to a dramatic increase in reliability and scale. With these advances, dozens and even thousands of designed proteins are automatically generated and screened. Nevertheless, the success rate, particular ...

WILEY2022

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

Sailan Shui

Synthetic biology aims to engineer cells as miniature biological devices to sense, process, and respond to exogenous stimuli. Protein switches are designed to sense and respond to various molecular queues in a fast and specific manner, which fits the requi ...

EPFL2022

Hetero-Bis-Conjugation of Bioactive Molecules to Half-Sandwich Ruthenium(II) and Iridium(III) Complexes Provides Synergic Effects in Cancer Cell Cytotoxicity

Paul Joseph Dyson, Lucinda Kate Batchelor, Mouna Hadiji

Four bipyridine-type ligands variably derivatized with two bioactive groups (taken from ethacrynic acid, flurbiprofen, biotin, and benzylpenicillin) were prepared via sequential esterification steps from commercial 2,2'-bipyridine-4,4'-dicarboxylic acid an ...

AMER CHEMICAL SOC2021

Novel broad-spectrum virucidal antivirals

Matteo Gasbarri

The current COVID-19 pandemic has showed the threats that viruses can cause to the whole world. Over 200 million infections and over 4.5 million deaths and enormous socio-economic impact were the output of the emergence of a single new pathogen: SARS-CoV-2 ...

EPFL2021

Targeting the oncogenic signaling of the transcription factor STAT3 with potent and selective monobody inhibitors

Grégory La Sala

Many targeted cancer therapies fail to improve the overall survival of patients. Limitations involve low drug selectivity and the rapid development of resistance. Moreover, the majority of oncogenic drivers presently remain considered as undruggable as th ...

EPFL2020

Biology and therapeutic targeting of tumour-associated macrophages

Tim Beltraminelli, Michele De Palma

Macrophages sustain tumour progression by facilitating angiogenesis, promoting immunosuppression, and enhancing cancer cell invasion and metastasis. They also modulate tumour response to anti-cancer therapy in pre-clinical models. This knowledge has motiva ...

WILEY2020

Modeling biochemical reaction networks in complex intracellular environments

Daniel Robert Weilandt

Whether one aims to design treatments for diseases such as cancer or diabetes, engineer cells to produce valuable biochemicals sustainably, or to grasp the behavior of living organisms, it is essential to understand how cells react to genetic, environmenta ...

EPFL2020

Clofarabine Commandeers the RNR-alpha-ZRANB3 Nuclear Signaling Axis

Yimon Aye, Yi Zhao

Ribonucleotide reductase (RNR) is an essential enzyme in DNA biogenesis and a target of several chemotherapeutics. Here, we investigate how antileukemic drugs (e.g., clofarabine [CIF]) that target one of the two subunits of RNR, RNR-alpha, affect noncanoni ...

CELL PRESS2020

Modeling, predicting and mining metabolism at atom-level resolution

Jasmin Maria Hafner

Living organisms can catalyze many thousands of biochemical reactions that they use to convert energy and matter, which provides them with the essentials for life. The sum of these chemical reactions happening in an organism is called metabo-lism. Understa ...

EPFL2020

Algorithms and flowchart for the design of synthetic biochemical networks

Homa Mohammadi Peyhani

New drugs are needed to assure effective therapies for previously untreated diseases, emerging diseases, and personalized medicine, but the process of drug development is complex, costly, and time-consuming. This is especially problematic considering that ...

EPFL2020

Lack of effect on ambulation of dalfampridine-ER (4-AP) treatment in adult SMA patients

Brian Donal McCabe

SMA is a genetically determined motor system disorder that results in muscle weakness, selective motor neuron death, muscle atrophy, and impaired functional mobility. In SMA model systems, long-term treatment with 4-aminopyridine (4-AP) has been shown to i ...

PERGAMON-ELSEVIER SCIENCE LTD2020

Enzyme annotation for orphan and novel reactions using knowledge of substrate reactive sites

Ljubisa Miskovic, Vassily Hatzimanikatis, Noushin Hadadi, Marianne Seijo

Thousands of biochemical reactions with characterized activities are “orphan,” meaning they cannot be assigned to a specific enzyme, leaving gaps in metabolic pathways. Novel reactions predicted by pathway-generation tools also lack associated sequences, l ...

National Academy of Sciences2019