AZD3463

SKU: orb1226459

Description

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.

Key Properties

• CAS Number: 1356962-20-3
• MW: 448.95
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₅ClN₆O
• SMILES: ClC1=CN=C(NC2=CC=C(N3CCC(N)CC3)C=C2OC)N=C1C4=CNC5=C4C=CC=C5
• Target: ALK
• Solubility: DMSO: 24 mg/mL (53.45 mM)

Bioactivity

• In Vivo:
  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.
• 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. Cell Proliferation Assay Cell line: IMR-32, NGP, NB-19, SH-SY5Y, SK-N-AS and LA-N-6 cells. Concentration: 0-50 μM. Incubation time: 72 h. Result: 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AZD3463 | AZD 3463 | AZD-3463

Quick Database Links

Gene Symbol

ALK