Ingenol mebutate

Bezeichnung:Ingenol mebutate

CAS-Nr75567-37-2

Englisch Name:Ingenol mebutate

CBNumberCB92650628

SummenformelC25H34O6

Molgewicht430.53

MOL-Datei75567-37-2.mol

Ingenol mebutate physikalisch-chemischer Eigenschaften

Siedepunkt	576.9±50.0 °C(Predicted)
Dichte	1.26±0.1 g/cm3(Predicted)
storage temp.	-20°C
Löslichkeit	DMSO: soluble15mg/mL, clear
Aggregatzustand	powder
pka	11.52±0.70(Predicted)
Farbe	white to beige
Wasserlöslichkeit	Soluble in 100% ethanol, DMSO, dichloromethane, and methanol. Insoluble in water.
Stabilität	Stable for 1 year as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
InChIKey	VDJHFHXMUKFKET-WDUFCVPESA-N
SMILES	C(O[C@@H]1[C@@]2(O)[C@H](O)C(CO)=C[C@]3([H])C(=O)[C@]2(C=C1C)[C@H](C)C[C@@]1([H])C(C)(C)[C@]13[H])(=O)/C(/C)=C\C

Sicherheit

Giftige Stoffe Daten

75567-37-2(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Bildanzeige (GHS)
Alarmwort

Achtung
Gefahrenhinweise

H300：Lebensgefahr bei Verschlucken.

H314：Verursacht schwere Verätzungen der Haut und schwere Augenschäden.

H330：Lebensgefahr bei Einatmen.
Sicherheit

P260：Dampf/Aerosol/Nebel nicht einatmen.

P264：Nach Gebrauch gründlich waschen.

P264：Nach Gebrauch gründlich waschen.

P270：Bei Gebrauch nicht essen, trinken oder rauchen.

P271：Nur im Freien oder in gut belüfteten Räumen verwenden.

P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

P284：Atemschutz tragen.

P301+P310：BEI VERSCHLUCKEN: Sofort GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

P301+P330+P331：BEI VERSCHLUCKEN: Mund ausspülen. KEIN Erbrechen herbeiführen.

P303+P361+P353：BEI BERÜHRUNG MIT DER HAUT (oder dem Haar): Alle kontaminierten Kleidungsstücke sofort ausziehen. Haut mit Wasser abwaschen oder duschen.

P304+P340：BEI EINATMEN: Die Person an die frische Luft bringen und für ungehinderte Atmung sorgen.

P305+P351+P338：BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

P310：Sofort GIFTINFORMATIONSZENTRUM/Arzt/ anrufen.

P320：Besondere Behandlung dringend erforderlich

P321：Besondere Behandlung

P330：Mund ausspülen.

P363：Kontaminierte Kleidung vor erneutem Tragen waschen.

P403+P233：An einem gut belüfteten Ort aufbewahren. Behälter dicht verschlossen halten.

P405：Unter Verschluss aufbewahren.

P501：Inhalt/Behälter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen.

Ingenol mebutate Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Originator
Peplin (United States)
Verwenden
Ingenol 3-Angelate is used as a PKC activator, anticancer, and immunostimulant compound. It is also used to exhibits antileukemic activity, induces nuclear translocation of PKCδ, and induces apoptosis in acute myeloid leukemia (AML) cell lines and primary AML blast cells. Also displays antiproliferative effects and induces apoptosis in Colo205 cells.
Verwenden
Ingenol 3-Angelate is known to exhibit antitumor activities which induces plasma membrane and mitochondrial disruption and necrotic cell death.
Definition
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.
Trademarks
Picato
Biochem/physiol Actions
Ingenol-3-angelate, is a phorbol ester-like compound or a diacylglycerol analog that is used in the treatment of several disorders like skin cancer. It is also known as PEP005. Ingenol-3-angelate stimulates the initiation of the enzyme by providing PKCs (protein kinase C) to cellular membranes.
Clinical Use
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.
Synthese
Although several synthetic approaches to the ingenol family of terpenes have been reported,97-113 Liang and coworkers at LEO Pharma have reported a semisynthesis of the API from naturally-occurring ingenol. This natural product?ˉs accessibility from the seeds of E. lathyris renders it widely commercial on scale. The conversion of ingenol to ingenol mebutate involves a protection, esterification, and deprotection strategy to procure scale quantities of the drug.114 Conversion of ingenol (87) to the corresponding 5,20-acetonide 88 proceeded in good yield using a protocol modified from the original conditions described by Hecker. A considerable amount of study was conducted by Liang to affect efficient angeloylation with minimal isomerization of the double-bond to the corresponding Z-isomer (tiglate). It was found that angelic anhydride 89 (which is a commercially available reagent, but for process scale was prepared immediately prior to usage from the self-condensation of 99.5% pure angelic acid with 0.5 equivalents of DCC) in the presence of LHMDS gave acetonide 90 in over 95% conversion and was practically free of the undesired tiglate bi-product after recrystallization (73% yield).96 Deprotection of the acetonide 90 was affected using phosphoric acid and after three recrystallizations, ingenol mebutate (XIV) was produced on multigram scale in a combined yield of 37% starting from ingenol 87.
target
gp120/CD4 | HIV | PKC | P-gp | NF-kB | ERK
Lager
-20°C
Einzelnachweise
References/Citations

Ingenol mebutate Upstream-Materialien And Downstream Produkte

Ingenol mebutate Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

75567-37-2, Ingenol mebutate Verwandte Suche:

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