Design of target-seeking antifibrotic compounds

Methods in Enzymology
Tero A H Järvinen

Abstract

Selective delivery of drugs and biotherapeutics to the site of disease (synaphic targeting) has a number of advantages. First, the enhanced accumulation of the therapeutic compound at the target tissue increases drug efficacy without increasing side effects. Alternatively, the dose of the drug can be lowered to reduce the side effects. On the practical level, when a drug is difficult or expensive to make, being able to lower the dose may be the key to commercial viability. Certain targeting systems can change the distribution of the drug in a beneficial way. Examples include wider distribution and deeper penetration of the drug in the target tissue, active intracellular targeting when desirable, and even targeting to a particular subcellular organelle. In this chapter, we illustrate these principles by describing the development of a targeting system for an antifibrotic biotherapeutic, decorin. The system is based on vascular homing peptide (sequence: CARSKNKDC; referred to as CAR) that specifically recognizes angiogenic blood vessels in injured (regenerating) and inflammatory tissues and can deliver a payload to such tissues with high selectivity. So far, the CAR-targeted decorin has been shown to promote tissue repair with re...Continue Reading

Citations

Dec 24, 2015·BioMed Research International·Tero A H Järvinen, Stuart Prince
Oct 6, 2015·International Journal of Molecular Sciences·Tero A H JärvinenStuart Prince
Nov 24, 2018·Free Radical Research·Thu Thi VuJin Han
Jun 5, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Toini PemmariYanling Liao
Jul 10, 2017·ACS Biomaterials Science & Engineering·Tero A H JärvinenFakhrul Ahsan

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