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PI3K MODULATORS

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Identification and characterisation of new class of PI3K modulators in oncology

PI3K signalling is a critical regulator of many cellular functions including cell growth and survival, and is deregulated in cancer and auto-immunity. This proposal is based on the concept to cause cell death by hyperactivating s... ver más

30/04/2021

UNIVERSITY COLLEGE...

213K€

Presupuesto del proyecto: 213K€

Líder del proyecto

UNIVERSITY COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-04-30

MSCA-IF-2018: Individual Fellowships

I+D

Cerrada hace 6 años

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

1 Participantes

UNIVERSITY COLLEGE LONDON

212.93K€ | Lider

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Duración del proyecto: 24 meses Fecha Inicio: 2019-04-10
Fecha Fin: 2021-04-30

Líder del proyecto

UNIVERSITY COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 213K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto PI3K signalling is a critical regulator of many cellular functions including cell growth and survival, and is deregulated in cancer and auto-immunity. This proposal is based on the concept to cause cell death by hyperactivating signalling in cancer cells above a tolerable threshold. This idea has been previously proposed for other kinases, but no small-molecule activators were available to formally test the idea. This proposal focuses on activators of the leukocyte-enriched PI3Kd, an isoform of PI3K that is involved in immune regulation and haematological malignancies. The 3 key objectives and their approaches are: 1. To discover and characterise small-molecule PI3Kd activators. This will be achieved using a combination of virtual screening and high throughput screening. 2. To understand the mechanism of PI3Kd activation. This enables understanding of how these activators function, and provides structural data that can be used for structure-based design and compound improvement. This will be achieved using structural biology (HDX-MS and crystallography), biochemical (lipid kinase) and biophysical (binding) assays. 3. To determine the activity of PI3Kd activators in haematopoietic malignancies. In order to use PI3Kd activators in cancer therapy, it is critical to determine the conditions under which hyperactivation of PI3Kd results in cancer cell death. This will be achieved with a panel of B and T-cell lymphoma cell lines using cell viability assays under different conditions. These objectives integrate my expertise in compound screening, molecular modelling and compound design with the world-leading expertise of the Host Lab in PI3K signalling, cancer biology and drug development. This proposal aims to make breakthroughs in understanding PI3K signalling, its exploitation in drug development and in cancer-therapy. This will be a key turning point in my scientific career and facilitate PI3K drug development collaborations of the Host Lab with the pharmaceutica.

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