1356962-20-3 Usage
Description
ALK/IGF1R inhibitor, specifically AZD3463, is a novel dual inhibitor that targets both the anaplastic lymphoma kinase (ALK) and insulin-like growth factor 1 receptor (IGF1R) pathways. It is designed to overcome multiple mechanisms of acquired resistance to Crizotinib, a tyrosine kinase inhibitor used in the treatment of certain types of cancer. By inhibiting these two pathways, ALK/IGF1R inhibitor plays a crucial role in disrupting cancer cell growth and survival, making it a promising therapeutic agent in oncology.
Uses
Used in Oncology:
ALK/IGF1R inhibitor is used as an anticancer agent for addressing resistance mechanisms in cancer treatment. It is particularly effective against tumors that have developed resistance to Crizotinib, a commonly used tyrosine kinase inhibitor. By targeting both ALK and IGF1R pathways, the inhibitor can potentially overcome resistance and improve treatment outcomes for patients with various types of cancer.
Used in Drug Resistance Research:
In the field of drug resistance research, ALK/IGF1R inhibitor is used to study the mechanisms of acquired resistance to Crizotinib and other tyrosine kinase inhibitors. This research can help in the development of new strategies and therapies to combat drug resistance, ultimately improving the effectiveness of cancer treatments.
Used in Drug Development:
ALK/IGF1R inhibitor is also used in the development of new cancer therapies. Its dual targeting approach can serve as a model for designing future inhibitors that target multiple pathways simultaneously, potentially leading to more effective treatments with fewer side effects.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 1356962-20-3 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,3,5,6,9,6 and 2 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1356962-20:
(9*1)+(8*3)+(7*5)+(6*6)+(5*9)+(4*6)+(3*2)+(2*2)+(1*0)=183
183 % 10 = 3
So 1356962-20-3 is a valid CAS Registry Number.
1356962-20-3Relevant articles and documents
CHEMICAL COMPOUNDS
-
Page/Page column 39, (2012/02/06)
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