Trametinib

Trametinib Struktur
871700-17-3
CAS-Nr.
871700-17-3
Englisch Name:
Trametinib
Synonyma:
GSK-1120212;TraMetinib API;Mekinist trametinib;Trametinib free base;N-(3-{3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)aMino]-6,8-diMethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyriMidin-1(2H)-yl}phenyl)acetaMide;CS-30;100836;Mekinist);TraMetinib;QuMei iMatinib
CBNumber:
CB32514557
Summenformel:
C26H23FIN5O4
Molgewicht:
615.39
MOL-Datei:
871700-17-3.mol

Trametinib Eigenschaften

Schmelzpunkt:
300-301 °C
Dichte
1.74
storage temp. 
-20°C
Löslichkeit
Soluble in DMSO (up to 20 mg/ml)
Aggregatzustand
White solid.
pka
14.76±0.70(Predicted)
Farbe
White
Stabilität:
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
Sicherheit
  • Risiko- und Sicherheitserklärung
  • Gefahreninformationscode (GHS)
S-Sätze: 24/25
HS Code  29339900
Bildanzeige (GHS) GHS hazard pictograms
Alarmwort Achtung
Gefahrenhinweise
Code Gefahrenhinweise Gefahrenklasse Abteilung Alarmwort Symbol P-Code
H317 Kann allergische Hautreaktionen verursachen. Sensibilisierung der Haut Kategorie 1A Warnung P261, P272, P280, P302+P352,P333+P313, P321, P363, P501
H361 Kann vermutlich die Fruchtbarkeit beeinträchtigen oder das Kind im Mutterleib schädigen. Reproduktionstoxizität Kategorie 2 Warnung P201, P202, P281, P308+P313, P405,P501
H372 Schädigt bei Hautkontakt und Verschlucken die Organe bei längerer oder wiederholter Exposition. Spezifische Zielorgan-Toxizität (wiederholte Exposition) Kategorie 1 Achtung P260, P264, P270, P314, P501
Sicherheit
P201 Vor Gebrauch besondere Anweisungen einholen.
P202 Vor Gebrauch alle Sicherheitshinweise lesen und verstehen.
P260 Dampf/Aerosol/Nebel nicht einatmen.
P261 Einatmen von Staub vermeiden.
P264 Nach Gebrauch gründlich waschen.
P264 Nach Gebrauch gründlich waschen.
P270 Bei Gebrauch nicht essen, trinken oder rauchen.
P272 Kontaminierte Arbeitskleidung nicht außerhalb des Arbeitsplatzes tragen.
P280 Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.
P281 Vorgeschriebene persönliche Schutzausrüstung verwenden.
P302+P352 BEI BERÜHRUNG MIT DER HAUT: Mit viel Wasser/... (Hersteller kann, falls zweckmäßig, ein Reinigungsmittel angeben oder, wenn Wasser eindeutig ungeeignet ist, ein alternatives Mittel empfehlen) waschen.
P308+P313 BEI Exposition oder falls betroffen: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.
P321 Besondere Behandlung
P333+P313 Bei Hautreizung oder -ausschlag: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.
P363 Kontaminierte Kleidung vor erneutem Tragen waschen.
P405 Unter Verschluss aufbewahren.
P501 Inhalt/Behälter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen.

Trametinib Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung

Trametinib is an inhibitor of MEK1 and -2. It inhibits B-RAF- and C-RAF-induced phosphorylation of MEK1 (IC50s = 3.4 and 1.8 nM, respectively) and MEK2 (IC50s = 1.6 and 0.92 nM, respectively). Trametinib inhibits the growth of two human colorectal cancer cell lines expressing mutant B-RAF (IC50s = 0.48 and 0.52 nM) and seven cell lines expressing mutant K-Ras (IC50s = 2.2-174 nM) but does not inhibit the growth of wild-type COLO 320DM cells expressing both B-RAF and K-Ras (IC50 = >10,000 nM). It reduces tumor growth in HT-29 and COLO 205 mouse xenograft models when used at doses of 0.3 and 1 mg/kg per day. Trametinib (0.03 and 0.1 mg/kg per day) also decreases M. tuberculosis-induced increases in hind paw volume in a rat model of arthritis. Formulations containing trametinib, in combination with dabrafenib, have been used in the treatment of metastatic mutant B-RAFV600E melanoma.

Verwenden

Used in the systematic treatment of advanced cutaneous melanoma. An EGFR kinase inhibitor.

Indications

MEK, also known as MAPK, is a dual specificity threonine/tyrosine kinase that is a key node in the Raf–Ras–MEK signaling pathway. Small-molecule MEK inhibitors represent the largest group of type III allosteric inhibitors that do not bind to the ATP binding pocket. As of December 2016, besides the FDA-approved MEK1/2 inhibitors trametinib (Mekinist(R), GlaxoSmithKline) and cobimetinib (Cotellic(R), Roche), over 10 MEK inhibitors are currently in clinical trials. Trametinib was approved by FDA in 2013 for the treatment of patients with either B-Raf V600E or V600K mutated metastatic melanoma. Considering the fact that MEK and Raf are different kinases along the same pathway of Ras–Raf–MEK/ERK signaling cascade, combination strategies using both MEK and B-Raf inhibitors were utilized to overcome the observed progression using single-agent trametinib, which usually occurs within 7months. FDA approved the combination of trametinib and dabrafenib for the treatment of B-Raf V600E/K mutated metastatic melanoma in January 2014 and the combination of cobimetinib and vemurafenib for the same type of indication. Although significant improvement in progression-free survival was observed using MEK/B-Raf combination strategy, the incidence of some common adverse effects, such as vomiting, diarrhea, nausea, rash, and pyrexia, also increased.

Definition

ChEBI: A pyridopyrimidine that is used (as its dimethyl sulfoxide addition compound) for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, and who have not received prior BRAF inhibitor treatment.

Clinical Use

Trametinib (GSK1120212) is an oral MEK inhibitor which has demonstrated excellent results in combination therapy for BRAF-mutated melanoma and is FDA approved in combination with BRAF inhibitors for that indication. Trametinib was evaluated initially as a single agent in KRAS mutant NSCLC in comparison with docetaxel and pemetrexed. Results as a single agent were not impressive, with an ORR of only 12% in these patients.

Trametinib Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte


Trametinib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global( 312)Lieferanten
Firmenname Telefon E-Mail Land Produktkatalog Edge Rate
BIONNA MEDICINE CO.,LTD
01056380788-8515; +8618518759099
790226113@qq.com China 52 58
Henan Tianfu Chemical Co.,Ltd.
+86-0371-55170693 +86-19937530512
info@tianfuchem.com China 21703 55
Hangzhou FandaChem Co.,Ltd.
008657128800458; +8615858145714
fandachem@gmail.com China 9359 55
Nanjing ChemLin Chemical Industry Co., Ltd.
025-83697070
product@chemlin.com.cn CHINA 3012 60
Nanjing Finetech Chemical Co., Ltd.
025-85710122 17714198479
sales@fine-chemtech.com CHINA 885 55
ATK CHEMICAL COMPANY LIMITED
+undefined-21-51877795
ivan@atkchemical.com China 32480 60
career henan chemical co
+86-0371-86658258
sales@coreychem.com China 29919 58
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 967 58
HubeiwidelychemicaltechnologyCo.,Ltd
18627774460
faith@widelychemical.com CHINA 742 58
Hubei xin bonus chemical co. LTD
86-13657291602
linda@hubeijusheng.com CHINA 22968 58

  • N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]acetamide GSK-1120212
  • Trametinib (GSK1120212,JTP 74057)
  • Trametinib, >=98%
  • Acetamide, N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]-
  • N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-tri
  • N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]acetamide
  • TraMetinib
  • GSK-1120212(traMetinib,JTP-74057)
  • JTP-74057, GSK212, TRAMETINIB
  • GSK1120212 (JTP-74057)
  • TraMetinib/GSK1120212
  • GSK1120212 ,TraMetinib
  • GSK1120212 (JTP-74057, TraMetinib)
  • N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)aMino]
  • GSK-1120212 N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]acetamide
  • QuMei iMatinib
  • CS-30
  • Trametinib Impurity
  • 100836
  • Trametinib, 98%, a MEK1/2 inhibitor
  • N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide
  • Trametinib (GSK1120212,JTP 74058)
  • Trametinib USP/EP/BP
  • Trametinib Trametinib
  • Mekinist)
  • N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7...
  • N-[3-[3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyr
  • Mekinist trametinib
  • TraMetinib API
  • GSK-1120212
  • Trametinib free base
  • Sibutramine for,
  • N-(3-{3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)aMino]-6,8-diMethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyriMidin-1(2H)-yl}phenyl)acetaMide
  • inhibit,MAP2K,Apoptosis,Autophagy,GSK-1120212,Inhibitor,orally,GSK 1120212,type,MAPKK,collageninduced,MEK,Trametinib,arthritis,JTP74057,AIA,JTP 74057,Mitogen-activated protein kinase kinase,Adjuvant-induced,CIA
  • Valine Impurity 13
  • 871700-17-3
  • 871700-17-4
  • C26H23FIN5O4
  • C26H23O4N5FI
  • Inhibitors
  • Anti-cancer&immunity
  • MAPK
  • API
  • Inhibitor
  • Pharmaceutical
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