Ingenol Disoxate: A Novel 4-Isoxazolecarboxylate Ester of Ingenol with Improved Properties for Treatment of Actinic Keratosis and Other Non-Melanoma Skin Cancers.

Authors: Bertelsen M, Stahlhut M, Grue-Sørensen G, Liang X, Bach Christensen G, Skak K, Engell KM, Högberg T
Publication: Dermatol Ther (Heidelb)
Keywords: animal tumor models, antiproliferative, chemical stability, cytotoxicity, ingenol derivatives, pro-inflammatory, regiocontrolled syntheses, skin cancer
Software: ADMET Predictor®

Introduction

Ingenol mebutate gel (Picato®, LEO Pharma A/S) is approved for the field treatment of actinic keratosis and is characterized by high sustained clearance of actinic lesions. The inherent propensity of ingenol mebutate towards chemical rearrangement necessitates refrigeration of the final product. We sought to identify novel ingenol derivatives with enhanced chemical stability and similar or improved in vitro potency and in vivo efficacy.