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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). University of Antwerp

Bert Maes
Theory and Spectroscopy of Molecules and Materials (TSM²), Molecular Spectroscopy (MolSpec), Leiden University Medical Center, Medical University of Vienna, University of Copenhagen, Leiden University, Pantheon-Sorbonne University, Organic synthesis (ORSY)
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 ...

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). University of Antwerp

Paul Cos
Leiden University Medical Center, Medical University of Vienna, University of Copenhagen, Leiden University, Pantheon-Sorbonne University, Laboratory for Microbiology, Parasitology and Hygiene (LMPH)
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 ...

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). University of Antwerp

Koen Augustyns
Leiden University Medical Center, Medical University of Vienna, University of Copenhagen, Leiden University, Pantheon-Sorbonne University, Medicinal Chemistry (UAMC)
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 ...

Ontogeny of cytochrome P450 activity in the zebrafish: an in vitro investigation. University of Antwerp

Steven Van Cruchten
Comparative Perinatal Development (CoPeD)
The zebrafish is increasingly used for toxicological purposes. However, knowledge on the biotransformation processes in this species is scarce, especially in zebrafish embryos which are increasingly used as an alternative model for teratogenicity screening of pharmaceuticals. In this project, we will assess the intrinsic activity of cytochrome P450 (CYPs) in adult male and female zebrafish and during embryonic development. This project will ...

Tackling functionality and balanced expression of cytochrome P450 enzymes: a generic toolbox for the production of specialized plant metabolites in bacteria Ghent University

Marjan De Mey
Department of Biotechnology

The natural diversity of plant metabolites, such as flavonoids, offers a plethora of attractive attributes through the decoration of a common skeleton. Oxygenation is the most commondecoration and is added in the final biochemical steps in the plant endoplasmic reticulum. Industrial production of these specialized flavonoids can be achieved chemically, through plant cell cultures or via extraction. These routes are paired with high costs and ...

Decipher cytochrome P450 enzymes (CYPs) by digital tools to produce flavonoids and terpenoids Ghent University

Marjan De Mey
Department of Biotechnology

Microbial production of plant metabolites has economic & environmental benefits over traditional extraction and chemical methods. Despite initial progress & the successful market introduction of some molecules, the microbial production of oxygenated plant metabolites (OPMs) mediated by cytochrome P450 enzymes (CYPs) is still lagging, making them almost inaccessible to society. In contrast, artificial intelligence (AI) & machine ...

Small heat shock proteins (HSPBs) sequestration at the outer mitochondrial membrane abrogates oxidative stress induced intrinsic apoptosis by preventing the release of cytochrome c from the mitochondria. University of Antwerp

Vincent Timmerman
Peripheral Neuropathies Group
Small heat shock proteins (HSPBs) are ATP-independent chaperones that are involved in maintaining the proteome integrity by preventing aberrant protein aggregation. They form highly dynamic, polydisperse oligomeric ensembles, and contain long intrinsically disordered regions. Experimental challenges posed by these aforementioned properties have greatly hindered our understanding of HSPBs. Unpublished work from our lab has shown that HSPBs ...

Progress novel assets (one FIH start) for nontubercular mycobacteria that may act synergistically with bedaquiline and cytochrome bc drugs (RespiriNTM). University of Antwerp

Koen Augustyns
Theory and Spectroscopy of Molecules and Materials (TSM²), Organic synthesis (ORSY), Molecular Spectroscopy (MolSpec), Leiden University Medical Center, Medical University of Vienna, University of Copenhagen, Leiden University, Pantheon-Sorbonne University, Medicinal Chemistry (UAMC)
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 ...

Interaction between Fusarium mycotoxins and cytochrome P450 drug metabolizing enzymes and ABC drug transporters in a porcine animal model Ghent University

Department of Pharmacology, Toxicology and Biochemistry

Mycotoxins are feed and food contaminants which can modulate the expression of genes encoding for CYP450 enzymes and ABC drug transporters and/or may modulate their activity. The goal of this research proposal is to investigate the effect of mycotoxin intake on the pharmacokinetic behavior of CYP450 and ABC substrate drugs in a pig animal model.

Construction and activity of recombinant cythochrome P450 enzymes as an in vitro system for reaction-phenotyping of drug candidates in the Göttingen minipig. University of Antwerp

Steven Van Cruchten
Molecular biophysics, physiology and pharmacology, Comparative Perinatal Development (CoPeD)
During drug development, pharmaceutical companies are required to characterize all routes of clearance (drug elimination) in man. Although the characterization of the metabolic profile of a drug is only required prior to the start of Phase 3 clinical trials, earlier information is very useful for the species selection in safety studies. Therefore, in vitro drug metabolism studies in several species are often performed early during drug ...