Drug Information

Drug (ID: DG01600) and It's Reported Resistant Information
Name
AZD3463
Synonyms
AZD3463; 1356962-20-3; AZD-3463; ALK/IGF1R inhibitor; N-(4-(4-Aminopiperidin-1-yl)-2-methoxyphenyl)-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine; N-[4-(4-aminopiperidin-1-yl)-2-methoxyphenyl]-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine; CS-1382; HY-15609; AZD 3463; C24H25ClN6O; N-(4-(4-aminopiperidin-1-yl)-2-methoxyphenyl)-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine.; KB-154896; SCHEMBL517412; GTPL7706; CHEMBL4203266; DTXSID50717792; EX-A328; CHEBI:167653; BDBM192752; HMS3653G05; AOB87394; BCP07685; 2238AH; NSC776787; s7106; ZINC95616580; AKOS026750287; CCG-269224; NSC-776787; NCGC00351596-09; AC-32961; AS-17033; DA-35311; QC-11775; FT-0749742; SW219925-1; F20803; Q27074737; ALK/IGF1R inhibitor; ; ; N-(4-(4-aminopiperidin-1-yl)-2-methoxyphenyl)-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine; N-[4-(4-amino-1-piperidinyl)-2-methoxyphenyl]-5-chloro-4-(1H-indol-3-yl)-2-pyrimidinamine
    Click to Show/Hide
Indication
In total 1 Indication(s)
Hepatitis C virus infection [ICD-11: 1E50-1E51]
Investigative
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Lung cancer [ICD-11: 2C25]
[1]
Target Hepatitis C virus Non-structural 5A (HCV NS5A) POLG_HCV1 [2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
5
IsoSMILES
COC1=C(C=CC(=C1)N2CCC(CC2)N)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl
InChI
InChI=1S/C24H25ClN6O/c1-32-22-12-16(31-10-8-15(26)9-11-31)6-7-21(22)29-24-28-14-19(25)23(30-24)18-13-27-20-5-3-2-4-17(18)20/h2-7,12-15,27H,8-11,26H2,1H3,(H,28,29,30)
InChIKey
GCYIGMXOIWJGBU-UHFFFAOYSA-N
PubChem CID
56599293
TTD Drug ID
D0LF5Q
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Brain cancer [ICD-11: 2A00]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: ALK tyrosine kinase receptor (ALK) [2]
Sensitive Disease Neuroblastoma [ICD-11: 2A00.11]
 Disease Info 
Molecule Alteration Missense mutation
p.F1174L (c.3520T>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.75  Å
PDB: 3AOX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.75  Å
PDB: 4FNW
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.34
TM score: 0.99391
Amino acid change:
F1174L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model IMR-32 cells Abdomen Homo sapiens (Human) CVCL_0346
Sk-N-AS cells Adrenal Homo sapiens (Human) CVCL_1700
SH-SY5Y cells Abdomen Homo sapiens (Human) CVCL_0019
NGP cells Lung Homo sapiens (Human) CVCL_2141
N b-19 cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Orthotopic Mouse Model of NB Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Colony formation assay
Key Molecule: ALK tyrosine kinase receptor (ALK) [2]
Sensitive Disease Neuroblastoma [ICD-11: 2A00.11]
 Disease Info 
Molecule Alteration Missense mutation
p.F1174L (c.3522C>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.75  Å
PDB: 3AOX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.75  Å
PDB: 4FNW
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.34
TM score: 0.99391
Amino acid change:
F1174L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
M
-
1070
|
Q
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M
-
E
-
L
-
Q
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1080
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model IMR-32 cells Abdomen Homo sapiens (Human) CVCL_0346
Sk-N-AS cells Adrenal Homo sapiens (Human) CVCL_1700
SH-SY5Y cells Abdomen Homo sapiens (Human) CVCL_0019
NGP cells Lung Homo sapiens (Human) CVCL_2141
N b-19 cells N.A. Homo sapiens (Human) N.A.
In Vivo Model Orthotopic Mouse Model of NB Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay; Colony formation assay
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Proto-oncogene c-Ros (ROS1) [1]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G2032R (c.6094G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot analysis; Conformational analysis
Experiment for
Drug Resistance		 CellTiter-96 AQueous One assay
References
Ref 1 Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitorsProc Natl Acad Sci U S A. 2015 Sep 29;112(39):E5381-90. doi: 10.1073/pnas.1515281112. Epub 2015 Sep 8.
Ref 2 Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosisSci Rep. 2016 Jan 20;6:19423. doi: 10.1038/srep19423.

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