CXCR4 modulating compounds for the treatment of medical disorders
- 技术优势
- •Existing small molecule CXCR4 modulators are all antagonists •The compounds described herein display unique agonist activity which may offera treatment for a variety of diseases with improved pharmacology such asreduced stem cell mobilization
- 详细技术说明
- CXCR4 Modulating Compounds for the Treatment of Medical Disorders
- *Abstract
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BACKGROUND
The chemokine CXCL12 (SDF-1) and its cognate receptor CXCR4 are involved in a large number of physiological processes including HIV infectivity, inflammation, tumorigenesis, stem cell migration, and autoimmune diseases. In many cases, small molecules have advantages over peptides and proteins as molecular probes and therapeutics due to improved metabolic stability, absorption, brain penetration, and decreased immunogenicity. It is therefore of great importance to develop new small molecule CXCR4 agonists and antagonists to study the biology of this receptor and to develop new therapeutics.
ABSTRACT
The chemokine CXCL12 (SDF-1) and its cognate receptor CXCR4 are involved in a large number of physiological processes including HIV infectivity, inflammation, tumorigenesis, stem cell migration, and autoimmune diseases. There has been one approved drug that targets CXCR4, an antagonist which is used for stem cell mobilization prior to autologous stem cell transplantation. However, this drug has the potential for several important side effects such as leukocytosis and possible effects on the cardiovascular system. New CXCR4-acting agents could provide therapeutics against a wide variety of diseases. Northwestern researchers have discovered the first known small molecule CXCR4 agonists. This small molecule used in several assays suggest therapeutic benefit, including cancer cell chemosensitization. The new agonist pharmacology demonstrated by these compounds has the potential to enable different types of in vivo effects different from known CXCR4 antagonists and allow for therapeutic targeting using CXCR4 for new indications.
- *Inventors
- Gary Schiltz* Richard Miller Rama Mishra
- *Publications
- MishraR, Shum A, Plantanias L, Miller RJ, Schiltz G (2016). Discovery andcharacterization of novel small-molecule CXCR4 receptor agonists andantagonists. Sci Rep. 6:30155.
- 国家/地区
- 美国
