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TRANSPORTERPGX

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Transporter pharmacogenomics the contribution of transporters to variability i...

Transporter pharmacogenomics the contribution of transporters to variability in drug response The response to drug therapy varies widely between individuals. Proteins involved in the absorption, distribution, metabolism and excretion of drugs play a central role in determining the concentration of a drug at the target site... ver más

31/01/2017

HELSINGIN YLIOPIST...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

HELSINGIN YLIOPISTO 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 FP7 notifico la concesión del proyecto el día 2017-01-31 No tenemos la información de la convocatoria

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1 Participantes

HELSINGIN YLIOPISTO

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Líder del proyecto

HELSINGIN YLIOPISTO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The response to drug therapy varies widely between individuals. Proteins involved in the absorption, distribution, metabolism and excretion of drugs play a central role in determining the concentration of a drug at the target site, and thus drug efficacy and toxicity. Transporters are membrane proteins that mediate the translocation of chemicals into and out of cells using active and passive mechanisms. We have identified a single nucleotide variant in the SLCO1B1 gene encoding the organic anion transporting polypeptide 1B1 (OATP1B1), which severely impairs the hepatic uptake of the cholesterol-lowering drug simvastatin leading to an increased systemic exposure to the drug, and a markedly increased risk of simvastatin-induced muscle toxicity. The effects of this variant differ significantly between statins, forming a rational basis for individualized lipid-lowering therapy. In addition to OATP1B1, also OATP1A2, OATP1B3, and OATP2B1 are known to transport several drugs in vitro (e.g., anticancer, cardiovascular and anti-infective drugs). However, the roles of these transporters in the pharmacokinetics of drugs in vivo in humans are unknown. The aim of this project is to systematically search for genetic variants of SLCO1A2, SLCO1B3 and SLCO2B1, which have functional significance in vivo in humans. This project will enable studies to determine the roles of these transporters in the pharmacokinetics of drugs and in the disposition of endogenous compounds in vivo, with implications for drug development and drug safety. Moreover, functionally significant variants in these genes may be used to personalize drug therapies. Overall, the project can significantly facilitate the development of new drugs and can improve the safe and effective use of drugs already in clinical use, thus increasing the health and well-being of mankind and reducing the overall costs of healthcare and drug development.

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