Short-chain fatty acid hexosamine analogs and their use in tissue engineering applications

US10227369B2 · kind B2 · utility

Assignee

• THE JOHNS HOPKINS UNIVERSITY · US

Inventors

• Jennifer H. Elisseeff · Baltimore, US
• Kevin J. Yarema · Albany, US
• Jeannine Coburn · Baltimore, US
• Udayanath Aich · Baltimore, US

Key dates

• Filing date: Mar 11, 2014
• Grant date: Mar 12, 2019
• Expiry date: Jan 22, 2035

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K45/06
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A new class of molecules, C1—OH tributanoylated hexosamines, including, for example, GalNAc, GlcNAc and ManNAc, are demonstrated to increase cartilage-like tissue accumulation by IL-1β-stimulated chondrocytes. Furthermore, all three molecules reduced NFKB1 and IκBα driven gene expression, consistent with NFκB inhibitory properties of these analogs. GalNAc-a exposure produced the greatest ECM accumulation by IL-1β-stimulated chondrocytes. However, GalNAc-a exposure produced an opposite effect on MSC exposure, where a decrease in ECM accumulation was observed. These findings are in support of the function of NFκB signaling during limb development and growth plate chondrogenesis. The present invention shows the capability of this new class of hexosamine analogs as disease-modifying agents for treating cartilage damage.