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Development of dual-targeting epigenetic modulators for polypharmacology-based c...

Development of dual-targeting epigenetic modulators for polypharmacology-based cancer therapy Cancer is a multifactorial disorder involving different genetic and epigenetic alterations. Since epigenetic modifications are brought about by multiple enzymes working synergistically, multitargeting compounds may be particularly... see more

30/09/2024

UNIROMA1

173K€

Project Budget: 173K€

Project leader

UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

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Financing granted El organismo HORIZON EUROPE notifico la concesión del proyecto The day 2024-09-30

HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2024 ExpectedOutcome:

I+D

Cerrada does 9 months

0% 100% 100%

characteristics of the participant

Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

Private Information

No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

UNIROMA1

172.75K€ | Leader

UNIPV

N.D. | participant

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Project duration: 27 months Date Start: 2022-06-16
End date: 2024-09-30

Project leader

UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 173K€

participation deadline Sin fecha límite de participación.

Project description Cancer is a multifactorial disorder involving different genetic and epigenetic alterations. Since epigenetic modifications are brought about by multiple enzymes working synergistically, multitargeting compounds may be particularly effective to acutely interfere with aberrant processes. The simultaneous inhibition of two or more enzymes by a single molecule provides improved therapeutic efficacy compared to single-target inhibitors, along with reduced insurgence of drug resistance. Through this project, I aim at developing novel therapeutics targeting protein (de)methylation and (de)acetylation for application in cancer therapy. I will synthesise and evaluate hybrid molecules inhibiting two enzymes at the same time. I will develop two classes of compounds targeting the Lysine-specific histone demethylase 1A (LSD1) and either Protein arginine N-methyltransferase 5 (PRMT5) or Histone deacetylases 1-2 (HDAC1-2). These enzymes cooperate in different pathways that lead to cancer insurgence and progression, hence dual targeting represents a successful strategy to counteract tumour growth. To achieve the outlined aims, I will employ a multidisciplinary approach requiring the fusion of knowledge and tools from medicinal chemistry, biochemistry, biophysics, molecular and cell biology. Through the employment of cutting-edge synthetic approaches, I will prepare LSD1/PRMT5 and LSD1/HDAC1-2 inhibitors which will be assessed through multiple biochemical and biophysical assays. I will also employ native mass spectrometry to investigate their mode of action in the context of the multi-protein complexes formed by the protein targets. The most promising inhibitors will be evaluated in cellular assays to assess their anticancer properties and their effects on transcriptional regulation. This project will open innovative avenues for personalised therapies and provide additional weapons to overcome drug resistance, along with adding new knowledge on the epigenetic mechanisms of cancer.

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