AZD3463

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AZD3463 是一种新型口服生物可利用的 ALK 抑制剂，Ki 为 0.75 nM，也具有同等效力的 IGF1R 抑制作用。

AZD3463 is a novel orally bioavailable ALK inhibitor with Ki of 0.75 nM, which also inhibits IGF1R with equivalent potency.(In Vitro):AZD-3463 (0-50 μM; 72 h) suppresses the viability and proliferation of both wild type and mutant ALK NB cells.AZD-3463 (10 μM; 0-4 h) effectively inhibits ALK-mediated PI3K/AKT/mTOR signaling and induces apoptosis and autophagy in NB cells.AZD-3463 (0-100 nM; 4 h) inhibits FLT3-ITD-mediated activation of AKT, ERK1/2 and p38 in a dose-dependent manner in MOLM-13 and MV4-11 cells.(In Vivo):AZD3463 (15 mg/kg; i.p.; once daily for 2 days) inhibits tumor growth in different orthotopic NB xenograft mouse models.

AZD-3463 (0-50 μM; 72 h) suppresses the viability and proliferation of both wild type and mutant ALK NB cells.AZD-3463 (10 μM; 0-4 h) effectively inhibits ALK-mediated PI3K/AKT/mTOR signaling and induces apoptosis and autophagy in NB cells.AZD-3463 (0-100 nM; 4 h) inhibits FLT3-ITD-mediated activation of AKT, ERK1/2 and p38 in a dose-dependent manner in MOLM-13 and MV4-11 cells. Cell Proliferation AssayCell Line:IMR-32, NGP, NB-19, SH-SY5Y, SK-N-AS and LA-N-6 cells Concentration:0-50 μM Incubation Time:72 hResult:Inhibited IMR-32, NGP, NB-19, SH-SY5Y, SK-N-AS and LA-N-6 cells with IC50 values of 2.802, 14.55, 11.94, 1.745, 21.34 and 16.49 μM, respectively.Cell Autophagy Assay Cell Line:IMR-32, NGP , SH-SY5Y and SK-N-AS cells Concentration:10 μM Incubation Time:0-4 h Result:Potently inhibited or totally abolished the phosphorylation of Akt Ser473 and RPS6 Thr235/236.Induced cleavage of the autophagy marker LC3 A/BΙΙ within four hours.Apoptosis Analysis Cell Line:MOLM-13 and MV4-11 cells Concentration:0-100 nM Incubation Time:4 h (pretreat)Result:Selectively inhibited FLT3-ITD but not ligand-induced wild-type FLT3.

AZD3463 (15 mg/kg; i.p.; once daily for 2 days) inhibits tumor growth in different orthotopic NB xenograft mouse models. Animal Model:5 to 6-week-old female athymic Ncr nude mice (SH-SY5Y and NGP xenograft tumors bearing mice).Dosage:15 mg/kg Administration:Intraperitoneal injection; once daily for 2 days Result:Showed anti-tumor efficacy in both ALK WT and F1174L mutant orthotropic xenograft mouse models of NB.

AZD3463 | AZD 3463 | AZD-3463

Angiogenesis

ALK

ALK

Cancer

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1356962-20-3

448.95

C24H25ClN6O

>98% (HPLC)

DMSO: 24 mg/mL (53.45 mM)

ClC1=CN=C(NC2=CC=C(N3CCC(N)CC3)C=C2OC)N=C1C4=CNC5=C4C=CC=C5

N-(4-(4-aminopiperidin-1-yl)-2-methoxyphenyl)-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine.

(-20℃)

With Ice Pack

≥ 2 years