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
• Indication:
  In total 1 Indication(s)
  Hepatitis C virus infection [ICD-11: 1E50-1E51]; Investigative; [1]
• 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]
• 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

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: ALK tyrosine kinase receptor (ALK) [2]

• Molecule Alteration: Missense mutation; p.F1174L (c.3520T>C)
• Sensitive Disease: Neuroblastoma [ICD-11: 2A00.11]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: Sk-N-AS cells; Adrenal; Homo sapiens (Human); CVCL_1700
• In Vitro Model: SH-SY5Y cells; Abdomen; Homo sapiens (Human); CVCL_0019
• In Vitro Model: NGP cells; Lung; Homo sapiens (Human); CVCL_2141
• In Vitro Model: 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 blotting analysis
• Experiment for Drug Resistance: CCK-8 assay; Colony formation assay

Key Molecule: ALK tyrosine kinase receptor (ALK) [2]

• Molecule Alteration: Missense mutation; p.F1174L (c.3522C>A)
• Sensitive Disease: Neuroblastoma [ICD-11: 2A00.11]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: IMR-32 cells; Abdomen; Homo sapiens (Human); CVCL_0346
• In Vitro Model: Sk-N-AS cells; Adrenal; Homo sapiens (Human); CVCL_1700
• In Vitro Model: SH-SY5Y cells; Abdomen; Homo sapiens (Human); CVCL_0019
• In Vitro Model: NGP cells; Lung; Homo sapiens (Human); CVCL_2141
• In Vitro Model: 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 blotting analysis
• Experiment for Drug Resistance: CCK-8 assay; Colony formation assay

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene c-Ros (ROS1) [1]

• Molecule Alteration: Missense mutation; p.G2032R (c.6094G>A)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• 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 blotting 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.