Research team

Expertise

Computational chemistry Chemoinformatics Molecular modeling Computer-aided drug design Protein structure-based drug design Quantitative structure-activity relationships (QSAR)

Multi-Objective and Structure-Aware Generative Drug Design (MOSA). 01/11/2022 - 31/10/2024

Abstract

Current molecular design tools are mostly uni-objective by focusing on the optimization of one primary property using ligand-based models. In this project, we aim to develop AI-based molecular design tools for multi-objective molecular design that are aware of 3D structures of the receptor and ligand candidates which will reduce attrition due to unmet secondary objectives. The enrichment with structural data will also include injecting more physical knowledge in the interaction of protein-ligand designs by utilizing conformational sampling and model enrichment by learning from the quantum mechanical calculation of the molecular structures. The project will be organized into three work packages: 1) The first work package addresses tasks related to Integrating target structural information in predictive and generative models - 3D models: Introducing a new 3D DL model based on structural data of the ligand-receptor complex. This model can also be fine-tuned in downstream tasks for predicting structure related properties like affinity and IC50. - 4D models: Integration of the conformational flexibility into the model from the previous task. - Structure-based generative model: by using the latent space of the models (3D or 4D) to design new molecules with new novel interactions with the receptor 2) The second work package tackles tasks related to multi-objective molecule optimization - Introducing new shape/conformational energetic penalty/pharmacophoric scoring functions which can explicitly be implemented in an automatic differentiable framework to enable end-to-end the optimization process using the powerful DL optimizers. - Predictive2generative: use direct discrete gradient-based optimization or gradient-based distributional optimization to enable using predictive models for molecular optimization - Supervised molecular generator using controllable decoding models or via conditional generator 3) The third work package is related to Integrating the delivered models for the WPs 1&2 in a unified framework and applying above outcomes on real world drug design business applications across all therapeutic areas within Janssen.

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  • Research Project

Discovery of highly selective inhibitors and activity-based probes for dipeptidyl peptidase 9 (DPP9). 01/11/2021 - 31/10/2023

Abstract

Dipeptidyl peptidase 9 (DPP9) is a cytosolic serine protease. It is related to, among others, the diabetes drug target DPP4 and to DPP8. Especially DPP8 is highly homologous with DPP9 and both enzymes generally occur simultaneously in the cells. Recent research shows that DPP9 is an NLRP1-inflammasome inhibitor and, most notably, that DPP9 inhibition leads to inflammatory cell death (pyroptosis) in most Acute Myeloid Leukemia (AML) cell lines. This effect is also reproduced in mouse models of AML, indicating that DPP9-inhibition could be an innovative strategy to treat AML and related hematological malignancies. To date, only non-selective DPP8/9-inhibitors have been reported and these compounds are known to have toxicity and stability issues, limiting their application to preclinical settings. Recent, preliminary data obtained by the hosting labs show that specific structural modifications of the marketed DPP4 inhibitor vildagliptin, yields molecules with unprecedented selectivity for DPP9 over all related proteases. These molecules will be further optimized in this project to obtain analogues with maximized DPP9 selectivity. All molecules will be evaluated for DPP9 potency/selectivity. Selected representatives will be further investigated in cells and for the most promising molecule, in vivo pharmacokinetics will be determined in healthy mice. Finally, the most promising inhibitor will also be used as a structural template for activity-based biomarker probes of DPP9.

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  • Research Project

'ProVision3D: Feeling the e-Forces' - VR-ondersteund e-learning onderwijs aan de UA 15/10/2021 - 14/10/2022

Abstract

In our project, supported by the ESF at UAntwerpen, we model the course Chemo-Informatics and computational drug design into a blended course which includes the development of a VR tool. The form and structure are made in function of the phases of the learning process. In these phases of the learning process, we focus on various didactic components. Self-directed learning is paramount and students are expected to contribute to their own learning process at various moments. In the phase of searching, selecting and offering information, the student's activity is called upon. He builds up the necessary prior knowledge, individually or otherwise. The acquisition, processing and application can take place both offline and online. According to our standards, the search for an appropriate blend is crucial. A suitable blend must be a mix A suitable blend should be a mix of study materials, forms of work and assessment, and learning activities that contribute to the realisation of the learning objectives, a higher learning effect, and in which the students are motivated and challenged to do their best. In the context of this motivation, we want to deploy technological-didactic VR tools and an LMS platform that will make the delivery of the learning content (information) more tangible.

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  • Research Project

CRyo-EM STructure based Drug Design (CRYOSTUDIO). 01/05/2021 - 30/04/2023

Abstract

This project aims to understand in more detail how cryo-EM can be improved with computational methods that are integrated with the generation phase of the structures and assessing how these structures can have a different impact for molecular design and lead optimisation chemistry. By combining the J&J internal cryo-EM expertise with external physics-based computational expertise provided by University of Antwerpen and KTH (Sweden), and Janssen medicinal chemistry drug discovery, we expect to make significant contributions to selected discovery projects by predicting alternative protein conformations, understanding ligand binding sites and binding modes using cryo-EM, allowing us to better handle challenging structure-based drug design targets.

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  • Research Project

Fragment-based computational design of inhibitors of dipeptidyl peptidase 8 and 9. 01/11/2020 - 31/10/2024

Abstract

Evaluation of the binding affinity of small molecules against therapeutically relevant proteins is currently performed using in vitro assays tailored to the specific problem at hand. However, despite their proven usefulness, compound solubility issues and limited chemical diversity imposed by the input compound library, emphasise some drawbacks. Fragment-based methods have also been introduced in which fragments are linked up with other fragments to grow into drug-like molecules. However, because such fragments are small, binding is weak and not always straightforward to detect. Hence, as an alternative to the experimental fragment-based screening, this project is investigating whether it is possible to use computational fragment-based drug design to identify fragments that might serve as starting points for further optimisation. The proposed method utilises metadynamics of the protein in combination with a number of small fragments in an explicit water box. The validity of the method will be tested on three 'real-world' protein targets, including dipeptidylpeptidase 4 (DPP4), DPP8 and DPP9. The crystal structures of these three dimeric enzymes have been determined, and at UAMC we have synthesized a large number of inhibitors and have biochemically characterized their corresponding cross-reactivities (selectivities), hence allowing us to evaluate whether computational fragment-based design can be modified to address selectivity issues within the drug design cycle.

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  • Research Project

Progress novel assets (one FIH start) for nontubercular mycobacteria that may act synergistically with bedaquiline and cytochrome bc drugs (RespiriNTM). 01/05/2019 - 30/04/2025

Abstract

Non-tuberculous mycobacteria, such as Mycobacterium avium complex (MAC) and Mycobacterium abscessus, cause lung diseases resembling TB, mainly in immune-compromised patients or patients suffering from other lung diseases (e.g. cystic fibrosis). The incidence and prevalence of lung diseases caused by NTM are increasing worldwide. Importantly, in the US and Japan, as well as in other areas of the world where TB has declined, NTM disease is already at least three times more prevalent than TB. Treatment of NTM diseases relies on antibiotic combinations, however the drugs active against NTM are rather few and mainly different than those active against TB. These NTM treatments for the most common species (MAC and M. abscessus) are much less active than the current anti-TB regimen is for TB treatment. It is often necessary to administer antibiotic combinations for at least 12-24 months. The long and complex drug regimen that is currently recommended as a treatment against NTM-caused diseases carries the risk of inducing resistance in NTM. Several studies have already shown the existence and emergence of multidrug resistant NTM. The overall objective of RESPIRI-NTM is to find new drug candidates as potential components of a new, more efficient combination drug regimen against NTM that is less prone to resistance and allows shortening of treatment duration for NTM and multidrug-resistant NTM. Such a drug combination will synergistically target the energy metabolism of NTM or complementary targets. To achieve this, we will advance recently discovered inhibitors of the mycobacterial respiratory pathway. In addition, we will perform a novel, phenotypic screen in order to identify novel targets in NTM. Finally, we will also target host-factors that are essential for the intracellular survival of NTM. Together, we present a comprehensive plan to find novel strategies to combat non-tuberculous mycobacteria, shorten treatment time and reduce chances of drug resistance.

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  • Research Project

Progress new assets (one pre-new molecular entity and one first-time-in-human start) for tuberculosis that act synergistically with bedaquiline, cytochrome bc or cytochrome bd inhibitors (RespiriTB). 01/05/2019 - 30/04/2025

Abstract

Despite recent progress in biomedical research, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is still the world's leading infectious disease killer worldwide. Treatment options are limited, and expensive, recommended medicines are not always available in many countries, and patients experience many adverse effects from the drugs. Thus, there is an acute need for the development of a novel combination regimen with an indication for effective, shorter, and safer treatment of all forms of TB. The overall objective of RESPIRI-TB is to find new drug candidates as potential components of a new, more efficient combination drug regimen against TB that is less prone to resistance and allows shortening of treatment duration for TB, and multidrug-resistant TB. Such a drug combination will synergistically target the energy metabolism of Mtb or complementary targets. To achieve this, we will advance recently discovered inhibitors of the Mtb respiratory pathway. In addition, we will target the Mtb specific molecular mechanism that reduces reactive oxygen species in the cell.

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  • Research Project

Development of a comprehensive platform for targeting redox homeostasis in Mycobacterium tuberculosis. 01/01/2019 - 31/12/2022

Abstract

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a major public health hazard throughout the world and was responsible for more than 1.7 million deaths in 2016.The prevalence of drug resistance in Mtb calls for the legitimization of new and highly specific drug targets, focusing on unique pathways.The project encompasses a multidisciplinary approach to disturb the redox homeostasis in Mtb, in an effort to uncover new drug leads for fighting this deadly infection.

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  • Research Project

Towards the realization of a structural biology platform at the University of Antwerp: The Mosquito Xtal3 crystallization robot as the missing link. 01/01/2020 - 31/12/2021

Abstract

Despite the presence of a sound expertise, structural biology is currently not well-embedded within the University of Antwerp. Hence, UAntwerp researchers are dependent on collaborations with external partners to be productive and competitive in this field. Structural biology at UAntwerp will only successfully come of age by investing in the acquisition of basic infrastructure that will adequately support the existing expertise. In this project proposal, funding is requested for the purchase of the Mosquito Xtal3, a state-of-the-art crystallization robot that has become an indispensable workhorse in any structural biology laboratory. The Mosquito Xtal3 allows fast, robust and high-throughput crystallization of biological macromolecules, which is a basic requirement for structure determination through macromolecular X-ray crystallography.

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  • Research Project

Validation of the oxadiazolone isostere as a carboxylate replacement in caspase inhibitors: approaches involving Strecker-based synthetic methodology development and on-target strategies. 01/10/2018 - 30/09/2021

Abstract

Caspases are intracellular, aspartate selective cysteine proteases. Given their central role in cell death and inflammation, caspases have been studied intensively as drug targets to date. In spite of impressive preclinical results and significant investment in clinical evaluation, no caspase inhibitors have so far been approved as drugs by FDA or EMA. Two important reasons therefore are commonly cited: (1) The large structural homology of caspases that complicates the identification of selective compounds. (2) The limited biopharmaceutical quality of most compounds. Many contain an irreversible covalent warhead function that can potentially induce off-target effects. Most inhibitor families also contain a free carboxylate. Both the ionic character of this group and its potential for toxic metabolite formation, most probably discount critically on the permeability and ADME-Tox properties of inhibitors. Preliminary work at UAMC has identified the oxadiazolone moiety as a useful isosteric replacement for carboxylates in caspase inhibitors. Research in this proposal will validate this finding by introducing an oxadiazolone group in several relevant classes of caspase inhibitors. In addition, synthetic methodology based on the Strecker reaction will be elaborated. The latter will allow efficient access to caspase inhibitors with less reactive warhead types. Finally, drug discovery methodology will be developed that should allow "on-target" synthesis using caspase 1 as a model.

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  • Research Project

The Biomolecular Interaction Platform (BIP) at UAntwerp. 01/05/2018 - 30/04/2021

Abstract

Physical and functional interactions between biomolecules play pivotal roles in all aspects of human health and disease. Gaining a greater understanding of these biomolecular interactions will further expand our understanding of diseases such as cancer, metabolic diseases and neurodegeneration. At UAntwerp, 7 research groups have joined forces to obtain the absolutely necessary equipment to measure these interactions with a Biomolecular Interactions Platform (BIP). This will allow to detect interactions and precisely determine binding affinities between any kind of molecule, from ions and small molecules to high-molecular weight and multi-protein complexes. The BIP will also allow to identify collateral off- targets, crucial in the drug discovery field. Access to a BIP will strongly support ongoing research projects and bring research within the BIP-consortium to a higher level. Since biomolecular interactions are highly influenced by the methodology, it is recommended to measure the interaction by several, independent techniques and continue with the most appropriate one. For this reason, the consortium aims at installing a BIP, consisting of several complementary instruments that each measure biomolecular interactions based on different physical principles. They wish to expand the existing Isothermal Titration Calorimetry with two complementary state-of-the- art techniques: MicroScale Thermophoresis and Grating- Coupled waveguide Interferometry.

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  • Research Project

Synthesis of inhibitors and inhibitor-derived imaging probes for prolyl oligopeptidase (PREP) and dipeptidyl-peptidase (DPP9) with potential application in neurodegenerative disease. 01/01/2018 - 31/03/2022

Abstract

Prolyl oligopeptidase (PREP) and dipeptidyl-peptidase 9 (DPP9) are two related serine proteases. PREP is mainly expressed in the central nervous system. This proposal will focus on the possibility to inhibit aggregation of alpha-synuclein (alphaSYN) using active-site directed inhibitors of PREP. alphaSYN plays a key role in the pathophysiologies of Parkinson's and related diseases, where aggregates of alphaSYN precipitate as neurotoxic Lewy-bodies. There are currently no PREPinhibitors that are optimized to block alphaSYN aggregation and that have a biological profile that allows drug development. The proposal will therefore deliver optimized PREP inhibitors. In addition, a PREP-targeting imaging probe will be delivered to image (alphaSYN) in the brain. DPP9 has a wider expression in the human body than PREP, and is also present in the human brain. DPP9 is strongly linked to inflammatory processes, also in the context of neuro-inflammation. The latter is present in nearly all neurodegenerative diseases, including in synucleinopathies and Alzheimer's disease. It is also an early marker of disease that is present before symptoms appear. Of note, there are currently no selective DPP9 inhibitors available. Availability of the latter is essential to obtain preclinical validation of DPP9 inhibitors as novel agents that target neurodegeneration. In addition, the project aims to deliver a DPP9-selective probe for use in neurodegenerative disease imaging.

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  • Research Project

Computational investigations of the catalytic mechanism of Staphylococcus aureus transglycosylase: design and chemical synthesis of novel mechanism-based inhibitors. 01/10/2017 - 30/09/2021

Abstract

Bacterial resistance against current medications is a growing problem that will pose significant health problems in the near future. Penicillins are a class of antibiotics that exert there effect by blocking the biosynthesis of the bacterial cell wall by means of inhibition of the transpeptidase protein, an enzyme responsible for the synthesis of the essential glycan chains in the cell wall. An alternative approach to inhibit the growth of the bacterial cell wall would be by inhibition of the transglycosylase enzyme, a protein involved in the polymerisation of the sugar chains that make up the backbone of these glycan chains. Currently there are no medications on the market or in clinical trials that have a mechanism of action of glycosyltransferase inhibition, but it has been shown that blocking the normal function of this enzyme leads to inhibition of bacterial cell growth. The main objective of the current project is to identify potent inhibitors against this transglycosylase enzyme using large-scale molecular dynamics simulations to study the catalytic mechanism of action and kinetics in large detail. Results of these simulations will be used to propose novel chemical compounds that will be synthesized through a collaboration with the University of Leuven. Biochemical testing of the antibacterial effects of these compounds will be performed at the University of Liège.

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  • Research Project

Inhibitors of prolyl oligopeptidase (PREP) as novel candidates for tackling synucleinopathies: insight in structural, thermodynamic and kinetic parameters that determine inhibitor potential to block PREP-promoted alpha-Synuclein aggregation 01/10/2017 - 30/09/2020

Abstract

Inadequate perfusion, oxygen limitation and cell metabolic changes, are key factors contributing to the formation of an acidic microenvironment in tumors.1 Two pivotal adaptations of tumor cells, related to maintaining intracellular pH and homeostasis in an acidic environment, have recently received significant attention: (1) the presence of chronic autophagy and (2) the overexpression of carbonic anhydrases (CAs), mainly CA IX and CA XII. Aiming to counter these essential tumor survival processes, the proposal deals with discovering and thoroughly evaluating novel autophagy inhibitors and and dual [autophagy-CA] inhibitors. The following three Work Packages will be elaborated during the course of the project: 1) Biopharmaceutical optimization of the host's Atg4B-inhibitor set. 2) Design and synthesis of dual [Atg4B-CA] inhibitors. 3) Biological characterization of Atg4B- and hybrid [Atg4B-CA] inhibitors in acidic cancer cell cultures and in an animal model of colorectal cancer.

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  • Research Project

High-end molecular dynamics simulations combined with click chemistry synthesis to develop novel therapeutic compounds starting from small molecule fragments. 01/04/2017 - 31/03/2018

Abstract

Within the molecular modeling research group with UAMC we are evaluating and developing a number of computational approaches to design - in a de novo manner - novel small molecules with pharmacological properties. One such approach is the use of high-throughput molecular dynamics (MD) at atomic resolution and with the inclusion of explicit solvent. With this approach, the potential binding of small fragments towards therapeutic relevant proteins is explored using MD simulations at long timescales. The here presented project explores the potential benefits of combining experimental methods with in silico approaches, in casu the combination of click chemistry technologies with advanced molecular dynamics simulations of the movement and interactions of small fragments located in close proximity to a therapeutic protein of interest. Hence, extensive synthetic chemistry, internal biochemical testing and the combination of advanced molecular dynamics with molecular stereographics will be the main ingredients to a successful completion of this project.

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  • Research Project

Installing a center of excellence in the Central-Eastern region of Cuba to enhance production and research on bioactive plants. 01/01/2017 - 31/08/2022

Abstract

This project represents a formal research agreement between UA and on the other hand VLIR. UA provides VLIR research results mentioned in the title of the project under the conditions as stipulated in this contract. The aim of the project is to set-up a center of scientific excellence in the Central-Eastern region of Cuba for traditionally used bioactive plants and their metabolites.

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  • Research Project

On-target assembly of druglike small molecules as protease inhibitors: a bottom-up approach using urokinase plasminogen activator (uPA) as a model target. 01/10/2016 - 30/09/2019

Abstract

Common to all contemporary drug discovery strategies is that they revolve around iterative cycles of design, synthesis and potency evaluation, each time producing further optimized compounds. This is generally a very time- and cost-consuming process that could be significantly shortened by implementing so-called "on-target" strategies. The latter rely on direct assistance of the drug target, which serves as a physical template that selects useful drug fragments and assembles them into finalized ligands. In this way, synthesis and potency determination, along with aspects of molecular design, are merged into a single, time-efficient experimental step. This project aims to (1) expand the limited range of chemistry types that are currently known to be amenable to on-target approaches, (2) focusing on reactions that deliver "druglike" molecules. (3) In addition, computational models offering insight at the molecular level in on-target reactions will be developed to rationalize and refine the experimental approaches. As the model target for this project has been selected urokinase plasminogen activator (uPA), a daunting but highly promising drug target. The potential to deliver novel druglike, low nanomolar inhibitors of uPA will be used to assess the value of the on-target approaches. Given the status of uPA as a validated drug target, novel inhibitors of this enzyme have significant value for drug discovery.

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  • Research Project

Validation of the oxadiazolone isostere as a carboxylate replacement in caspase inhibitors: approaches involving Strecker-based synthetic methodology development and on-target strategies. 01/10/2016 - 30/09/2018

Abstract

Caspases are intracellular, aspartate selective cysteine proteases. Given their central role in cell death and inflammation, caspases have been studied intensively as drug targets to date. In spite of impressive preclinical results and significant investment in clinical evaluation, no caspase inhibitors have so far been approved as drugs by FDA or EMA. Two important reasons therefore are commonly cited: (1) The large structural homology of caspases that complicates the identification of selective compounds. (2) The limited biopharmaceutical quality of most compounds. Many contain an irreversible covalent warhead function that can potentially induce off-target effects. Most inhibitor families also contain a free carboxylate. Both the ionic character of this group and its potential for toxic metabolite formation, most probably discount critically on the permeability and ADME-Tox properties of inhibitors. Preliminary work at UAMC has identified the oxadiazolone moiety as a useful isosteric replacement for carboxylates in caspase inhibitors. Research in this proposal will validate this finding by introducing an oxadiazolone group in several relevant classes of caspase inhibitors. In addition, synthetic methodology based on the Strecker reaction will be elaborated. The latter will allow efficient access to caspase inhibitors with less reactive warhead types. Finally, drug discovery methodology will be developed that should allow "on-target" synthesis using caspase 1 as a model.

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  • Research Project

Discovery of necroptosis and ferroptosis inhibitors with potential applications in pathologies associated with regulated necrosis. 01/10/2016 - 30/09/2018

Abstract

The main objective of this research proposal is the discovery of novel chemical tool compounds to investigate the phenotype of necroptosis and ferroptosis at a molecular level in more detail. The use of such tool compounds will result in a better understanding of the different pathways of regulated necrosis, and will also demonstrate where therapeutic targeting is possible, ultimately leading to target identification and validation for novel and innovative treatment opportunities in diseases linked with inflammation and necrotic cell death.

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  • Research Project

On-target assembly of druglike small molecules: a bottom-up approach using urokinase plasminogen activator and caspase 1 as model targets. 01/01/2016 - 31/12/2019

Abstract

1) Current status in drug discovery methodology There are four commonly used approaches for the generation of "hits" and "leads" in contemporary drug discovery: (1) Structure-Activity-Relationship (SAR) research on high throughput screening (HTS) data, (2) transformation of endogenous ligands into druglike compounds, (3) in silico drug design and (4) fragment-based design. Due to the absence of a single eminent strategy, drug discovery projects often try implementing tailored aspects of several of these approaches simultaneously. Common to all these approaches is that lead molecules are produced from iterative cycles of design, synthesis and potency evaluation, each time producing further optimized compounds. This is generally a very time- and cost-consuming process that could be significantly shortened by implementing "on-target" strategies. The latter rely on direct assistance of the drug target, which serves as a physical template that selects useful drug fragments and assembles them into finalized ligands. In this way, synthesis and potency determination, along with aspects of molecular design, are merged into a single, time-efficient experimental step. Limited but convincing proof for the "on-target" drug design concept is present in literature and has relied on "click chemistry", reductive amination, hydrazone formation and disulfide exchange.1 In order to increase the practical value of on-target approaches for drug discovery, three factors are in our opinion required: (1) expansion of the range of (bio-orthogonal) chemistry types amenable to on-target approaches and, related to the former, (2) improvement of the "druglikeness" of the compound types that can be produced. (3) In addition, models offering insight into the fundamental kinetic and thermodynamic drivers of "on-target" reactions are, apart from one example, virtually absent from the scientific literature.2 2) Current status in drug discovery for urokinase plasminogen activator (uPA) and caspase 1. uPA and caspase 1 have been selected as the model targets for this work. Longstanding expertise in inhibitor discovery and biochemical screening exists for these targets at UAMC. In addition, both are generally considered as "daunting targets" for which drug discovery has proven challenging. uPA is a trypsin-like serine protease that is overexpressed in metastasizing solid tumors. The enzyme is a valuable oncology target but clinical development of its inhibitors has been problematic. This is most probably related to the doubtful biopharmaceutical quality of developed compounds and their insufficient selectivity with respect to other, phylogenetically related trypsin-like proteases.3 Likewise, selectivity issues have also been a constant concern with caspase 1 inhibitors. Caspase 1, also known as interleukin 1 converting enzyme (ICE) is a cysteine protease and a so-called "inflammatory caspase". Given its involvement in inflammasome formation, pyroptosis and necrosis, ICE is a validated drug target for a range of disorders characterized by inflammation and tissue remodeling. 4 B) Project Objectives 1) Developing reliable on-target versions of reaction types with high value for drug discovery. 2) Developing computational approaches to model and rationalize on-target reactions and their outcome. 3) Validating the technology by producing druglike inhibitors for uPA and caspase 1.

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  • Research Project

Rational design and synthesis of antagonists of the TSLP complex using chemo- and bioinformatics approaches. 01/01/2016 - 04/11/2018

Abstract

TSLP (thymic stromal lymphopoietin) is a pro-inflammatoir cytokine produced by the epithelial cells. It binds to its receptor called TSLPR. This project aims at developing a number of novel inhibitors which block the complexation of TSLP and TSLPR, using bio- en chemo-informatic tools.

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  • Research Project

Medicinal Chemistry-Drug Discovery (ADDN). 01/01/2015 - 31/12/2020

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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  • Research Project

Design and synthesis of TSLP complex antagonists based on chemo- and bio-informatics. 01/01/2015 - 31/12/2015

Abstract

Atopic diseases represent an important unmet need in modern day medicine. The pro-inflammatory cytokine TSLP is a key player in these pathologies. The aim of this project is the development of small molecules capable of disrupting TSLP signalling, using a chemo-and bio-informatics approach. These small molecules could help elucidate the role of TSLP in various pathologies and could be a starting point for further development of drugs targeting this pathway.

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  • Research Project

Discovery of necroptosis and ferroptosis inhibitors with potential applications in pathologies associated with regulated necrosis. 01/10/2014 - 30/09/2016

Abstract

The main objective of this research proposal is the discovery of novel chemical tool compounds to investigate the phenotype of necroptosis and ferroptosis at a molecular level in more detail. The use of such tool compounds will result in a better understanding of the different pathways of regulated necrosis, and will also demonstrate where therapeutic targeting is possible, ultimately leading to target identification and validation for novel and innovative treatment opportunities in diseases linked with inflammation and necrotic cell death.

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  • Research Project

An in-silico-based virtual screening of the compounds. 16/08/2014 - 16/09/2014

Abstract

This project represents a formal service agreement between UA and on the other hand VIB. UA provides VIB research results mentioned in the title of the project under the conditions as stipulated in this contract.

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  • Research Project