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Ingenol disoxate

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https://www.readbyqxmd.com/read/29296668/chemical-proteomics-identifies-slc25a20-as-a-functional-target-of-the-ingenol-class-of-actinic-keratosis-drugs
#1
Christopher G Parker, Christian A Kuttruff, Andrea Galmozzi, Lars Jørgensen, Chien-Hung Yeh, Daniel J Hermanson, Yujia Wang, Marta Artola, Steven J McKerrall, Christopher M Josyln, Bjarne Nørremark, Georg Dünstl, Jakob Felding, Enrique Saez, Phil S Baran, Benjamin F Cravatt
The diterpenoid ester ingenol mebutate (IngMeb) is the active ingredient in the topical drug Picato, a first-in-class treatment for the precancerous skin condition actinic keratosis. IngMeb is proposed to exert its therapeutic effects through a dual mode of action involving (i) induction of cell death that is associated with mitochondrial dysfunction followed by (ii) stimulation of a local inflammatory response, at least partially driven by protein kinase C (PKC) activation. Although this therapeutic model has been well characterized, the complete set of molecular targets responsible for mediating IngMeb activity remains ill-defined...
December 27, 2017: ACS Central Science
https://www.readbyqxmd.com/read/29204958/pharmacokinetics-and-safety-of-ingenol-disoxate-gel-administered-under-maximum-use-conditions-to-patients-with-actinic-keratosis
#2
Edward Lain, Torsten Skov, Anders Hall
BACKGROUND AND OBJECTIVES: Ingenol disoxate (LEO 43204) is a field therapy in development for the treatment of actinic keratosis (AK) on areas between 25 and 250 cm2. We evaluated the systemic exposure and safety of ingenol disoxate under maximum-use conditions. METHODS: This was a phase I, open-label, non-randomized, multicenter trial. Patients ≥ 18 years of age with ≥ 15 clinically typical, visible, discrete AK lesions in a treatment area on the full face or approximately 250 cm2 on the arm or scalp were treated once-daily for 3 consecutive days with ingenol disoxate 0...
December 4, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28264612/a-dose-finding-trial-with-a-novel-ingenol-derivative-ingenol-disoxate-leo-43204-for-field-treatment-of-actinic-keratosis-on-full-face-or-250%C3%A2-cm-2-on-the-chest
#3
Marc Bourcier, Linda Stein Gold, Lyn Guenther, Camilla M Andreassen, Johan Selmer, Gary Goldenberg
PURPOSE: Actinic keratoses (AKs) may progress to squamous cell carcinoma and can occur in cancerized fields as sub-clinical and clinically visible lesions. Ingenol disoxate gel is a topical field therapy for AK. This Phase I/II trial aimed to assess the safety and efficacy of ingenol disoxate on full face or chest in patients with AKs. MATERIALS AND METHODS: Part 1 was a phase-I, open-label, dose-escalation trial investigating the maximum tolerated dose of ingenol disoxate...
November 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28078678/a-seamless-phase-i-ii-dose-finding-trial-assessing-ingenol-disoxate-leo-43204-for-field-treatment-of-actinic-keratosis-on-the-scalp
#4
J Weiss, M Ulrich, M Bukhalo, M L Østerdal, B Bang, C W Hanke
BACKGROUND: Actinic keratosis (AK) is a common sun-related skin condition, which can progress to squamous cell carcinoma and occur in cancerized fields. OBJECTIVES: To investigate in a phase I/II trial the safety and efficacy of ingenol disoxate as topical field therapy for patients with AK on the balding scalp. METHODS: Part 1 was a phase I, open-label, dose-escalation trial investigating up to six doses of ingenol disoxate to determine the maximum tolerated dose (MTD)...
June 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/27503482/ingenol-disoxate-a-novel-4-isoxazolecarboxylate-ester-of-ingenol-with-improved-properties-for-treatment-of-actinic-keratosis-and-other-non-melanoma-skin-cancers
#5
Malene Bertelsen, Martin Stahlhut, Gunnar Grue-Sørensen, Xifu Liang, Gitte Bach Christensen, Kresten Skak, Karen Margrethe Engell, Thomas Högberg
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. METHODS: A number of ingenol esters were synthesized with full regiocontrol from ingenol...
December 2016: Dermatology and Therapy
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