3-アンゲリカ酸インゲノール 化学特性,用途語,生産方法
効能
抗悪性腫瘍薬
説明
Ingenol mebutate (also known as PEP005) was approved in January 2012
by the US FDA for the topical treatment of actinic keratoses (AK). Ingenol mebutate also received approval in 2012 in the European Union, Australia,
and Brazil for the same indication. Ingenol
mebutate, a diterpene ester natural product, is the active agent in the sap
of the plant Euphorbia peplus, which has long been used as a traditional remedy for skin lesions. Ingenol mebutate has a novel mechanism of action
involving initial plasma membrane disruption, rapid loss of mitochondrial
membrane potential, and cell death by primary necrosis within 1 h;
a subsequent tumor-specific immune response results in antibodydependent
cellular toxicity that eliminates residual cells. Ingenol mebutate
is obtained by extraction from the dried, milled aerial parts of Euphorbia peplus followed by a series of purification steps.
使用
Ingenol 3-Angelate is known to exhibit antitumor activities which induces plasma membrane and mitochondrial disruption and necrotic cell death.
定義
ChEBI: A tetracyclic diterpenoid ester obtained by formal condensation of the carboxy group of (2Z)-2-methylbut-2-enoic (angelic) acid with the 3-hydroxy group of ingenol. Used for the topical treatment of actinic keratosis.
臨床応用
Ingenol mebutate is a diterpene ester which was approved in the US, EU, Austrailia, and Brazil for the treatment of actinic keratosis, a disease stage associated with sun exposure which can potentially
develop into cancer. The drug, which is marketed by LEO Pharma A/S as Picato®, is administered as
a topical gel (0.015%, 0.05%) which has been proven effective in treating face-, scalp-, and trunklocalized
actinic keratosis in four randomized, double-blind, vehicle-controlled, multicenter studies.
The drug exhibits mild side effects limited to application-site conditions (e. g. irritation, pain, pruritus),
and no detectable concentrations of ingenol mebutate or two of its metabolites were found in blood
samples.94 Traditionally used as a home remedy for various skin conditions, the ingenol mebutate, also
referred to as ingenol 3-angelate, is the main active constituent of sap from the plant Euphorbia
pelpus.95 From natural extractions, 17 kg of fresh E. pelpus afforded 7 g of ingenol 3-angelate as an oil,
which upon further purification was deemed insufficient for process-scale production.
3-アンゲリカ酸インゲノール 上流と下流の製品情報
原材料
準備製品