Alectinib

Bezeichnung:Alectinib

CAS-Nr1256580-46-7

Englisch Name:Alectinib

CBNumberCB62534680

SummenformelC30H34N4O2

Molgewicht482.62

MOL-Datei1256580-46-7.mol

Alectinib physikalisch-chemischer Eigenschaften

Schmelzpunkt	274-276°C
Siedepunkt	722.5±60.0 °C(Predicted)
Dichte	1.28
storage temp.	-20°
Löslichkeit	Soluble in DMSO (up to 5 mg/ml with warming).
Aggregatzustand	solid
pka	13.70±0.40(Predicted)
Farbe	White
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions are not stable and should be prepared fresh daily.

Sicherheit

HS Code

2934999090

Gefahreninformationscode (GHS)

Alectinib Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Alectinib is another selective ALK inhibitor that is able to overcome resistance mutations from prior crizotinib exposure [38].
Chemische Eigenschaften
White to Off-White Solid
Verwenden
CH5424802 is a highly selective and potent anaplastic lymphoma kinase (ALK) inhibitor capable of blocking the resistant gatekeeper mutant, which results in reduced cell growth. CH5424802 have been clinically evaluated for the treatment of patients with ALK-driven tumors. Potent ALK inhibitor
Indications
Alectinib (Alecensa(R), Roche) was approved first in Japan in 2014 and then by US FDA in 2015 as a second-generation ALK inhibitor for NSCLC treatment on patients who have progressed or do not tolerate crizotinib. Developed through a structure-based drug design approach, alectinib is a benzocarbazolone derivative that has shown potent inhibitory activity against ALK (IC50 value of 1.9 nM) and gatekeeper mutant L1196M ALK (IC50 value of 1.6 nM). Alectinib is effective with crizotinib-resistant ALK mutations on L1196M, F1174L, R1275Q, and C1156Y. In addition, an array of small-molecule inhibitors are currently being evaluated by several clinical trials for ALK-driven tumors.
Definition
ChEBI: An organic heterotetracyclic compound that is 6,6-dimethyl-5,6-dihydro-11H-benzo[b]carbazol-11-one carrying additional cyano, 4-(morpholin-4-yl)piperidin-1-yl and ethyl substituents at positions 3, 8 and 9 respectively. Used (as the hydr chloride salt) for the treatment of patients with anaplastic lymphoma kinase-positive, metastatic non-small cell lung cancer.
Trademarks
Alecensa?
Allgemeine Beschreibung
Class: receptor tyrosine kinase; Treatment: NSCLC; Oral bioavailability = 37%; Elimination half-life = 33 h; Protein binding = >99%
in vitro
in cell free assays the ic50 of ch5424802 for enzyme activity of alk was 1.9 nm; the dissociation constant (kd) value for alk in an atp-competitive manner was 2.4 nm. the inhibitory activity for two hot spot-activating mutations (f1174l and r1275q) in neuroblastoma was comparable to that for wildtype alk [1].
in vivo
in the nci-h2228 model, oral administration of ch5424802 resulted in dose-dependent tumor growth inhibition (ed50 = 0.46 mg/kg) and tumor regression. moreover, treatment of 20 mg/kg ch5424802 showed rapid tumor regression and tumor regrowth did not occur throughout the 4-week drug-free period [2].
target
Primary targets: ALK (IC50 = 1.9 nM)/RET (IC50 = 4.8 nM)
Einzelnachweise
1) Sakamoto?et al.?(2011),?CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant; Cancer Cell,?19?679 2) Kodama?et al.?(2014),?Alectinib Shows Potent Antitumor Activity against RET-Rearranged Non-Small Cell Lung Cancer., Mol. Cancer Ther.?13?2910 3) Lu?et al.?(2017),?The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model; Cancer Lett,?400?61

Alectinib Upstream-Materialien And Downstream Produkte

Alectinib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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