Cortistatin analogues and syntheses and uses thereof

US10508121B2 · kind B2 · utility

Assignee

• President and Fellows of Harvard College · US

Inventors

• Matthew D. Shair · Lexington, US
• Juergen Ramharter · Wien, AT
• Henry Efrem Pelish · Newton, US
• Brian Bor-Jen Liau · Belmont, US
• Jae Young Ahn · Boston, US

Key dates

• Filing date: Mar 5, 2019
• Grant date: Dec 17, 2019
• Expiry date: Mar 5, 2039

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K16/26
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof.Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the □-catenin pathway, methods of modulating STAT 1 activity, methods of modulating the TGFβ/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.