1356962-20-3

Basic information

• Product Name: ALK/IGF1R inhibitor
• Synonyms: ALK/IGF1R inhibitor;AZD 3463;AZD3463;AZD-3463;N-[4-(4-Amino-1-piperidinyl)-2-methoxyphenyl]-5-chloro-4-(1H-indol-3-yl)-2-pyrimidinamine;2-Pyrimidinamine, N-[4-(4-amino-1-piperidinyl)-2-methoxyphenyl]-5-chloro-4-(1H-indol-3-yl)-;N-[4-(4-Amino-1-piperidinyl)-2-methoxyphenyl]-5-chloro-4-(1H-indol-3-yl)-2-pyrimidinamine AZD3463;N-(4-(4-Aminopiperidin-1-yl)-2-methoxyphenyl)-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine
• CAS NO: 1356962-20-3
• Molecular Formula: C₂₄H₂₅ClN₆O
• Molecular Weight: 448.9479
• Product Categories: Inhibitors
• Mol File: 1356962-20-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 723.6±70.0 °C(Predicted)
• Appearance: /
• Density: 1.338±0.06 g/cm3(Predicted)
• Solubility: insoluble in H2O; insoluble in EtOH; ≥11.22 mg/mL in DMSO
• PKA: 14.62±0.30(Predicted)
• CAS DataBase Reference: ALK/IGF1R inhibitor(CAS DataBase Reference)
• NIST Chemistry Reference: ALK/IGF1R inhibitor(1356962-20-3)
• EPA Substance Registry System: ALK/IGF1R inhibitor(1356962-20-3)

Safety Data

• Hazardous Substances Data: 1356962-20-3(Hazardous Substances Data)

Usage

Uses

AZD3463, is a novel ALK/IGF1R dual Inhibitor, having the ability of overcoming multiple mechanisms of acquired resistance to Crizotinib (C785000).

Biological Activity

azd3463 is a novel orally bioavailable alk/igf1r inhibitor with ki value of 0.75 nm. alk expression is largely restricted to neurons and upregulated in neuroblastoma. activated alk has been shown to promote cell survival and growth. high alk expression or mutations in the alk gene correlates with adverse outcomes in neuroblastoma. therefore, alk receptor tyrosine kinase is an important therapeutic target for drug development against neuroblastoma [1].

in vitro

azd3463 (5, 10, 20, and 50 μm) effectively inhibited the proliferation of neuroblastoma cell lines with wild type alk (wt) and alk activating mutations (f1174l and d1091n) via targeting the alk-mediated pi3k/akt/mtor pathway and ultimately induced apoptosis and autophagy in vitro. moreover, azd3463 (1 μm) significantly enhanced the cytotoxic effects of doxorubicin (1 μm) on neuroblastoma cells [1]. azd3463 simultaneously inhibited stat3 and akt to augment the cytotoxic effects of temozolomide and further reduce cell growth [2].

in vivo

azd3463 (15 mg/kg, i.p. injection) showed significant therapeutic efficacy on the growth of the neuroblastoma tumors with wt and f1174l oncogenic mutant alk in orthotopic xenograft mouse models [1].

target

alk, igf1r

IC 50

0.75 nm(ki)

references

1. wang y, wang l, guan s, cao w, wang h, chen z, et al. novel alk inhibitor azd3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis. sci rep. 2016;6:19423. 2. sampson vb, vetter ns, kamara df, collier ab, gresh rc, kolb ea. vorinostat enhances cytotoxicity of sn-38 and temozolomide in ewing sarcoma cells and activates stat3/akt/mapk pathways. plos one. 2015;10(11):e0142704.

Upstream product

• 937366-57-9 3-(2,5-dichloropyrimidine-4-yl)-1H-indole 
• 1356963-24-0 tert-butyl (1-(4-amino-3-methoxyphenyl)piperidin-4-yl)carbamate 

Relevant articles and documents

CHEMICAL COMPOUNDS

The present invention relates to compounds of Formula (I) and/or Formula (Ia): and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds inhibit ALK kinase activity, and thus may be used for the tr