Drug Information

Drug (ID: DG00270) and It's Reported Resistant Information
Name
Alectinib
Synonyms
1256580-46-7; CH5424802; CH 5424802; AF-802; Alecensa; UNII-LIJ4CT1Z3Y; AF 802; LIJ4CT1Z3Y; Alectinib (CH5424802); 9-ethyl-6,6-dimethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; CHEMBL1738797; AF802; 9-Ethyl-6,6-Dimethyl-8-[4-(Morpholin-4-Yl)piperidin-1-Yl]-11-Oxo-6,11-Dihydro-5h-Benzo[b]carbazole-3-Carbonitrile; 9-Ethyl-6,11-dihydro-6,6-dimethyl-8-[4-(4-morpholinyl)-1-piperidinyl]-11-oxo-5H-benzo[b]carbazole-3-carbonitrile; AK170451; C30H34N4O2; Alectinib; 9-ethyl-6,6-dimethyl-
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Indication
In total 1 Indication(s)
Lung cancer [ICD-11: 2C25]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
Brain cancer [ICD-11: 2A00]
[1]
Inflammatory myofibroblastic tumor [ICD-11: 2E92]
[2]
Lung cancer [ICD-11: 2C25]
[3]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Lung cancer [ICD-11: 2C25]
[4]
Diffuse large B-cell lymphoma [ICD-11: 2A81]
[5]
Target ALK tyrosine kinase receptor (ALK) ALK_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C30H34N4O2
IsoSMILES
CCC1=CC2=C(C=C1N3CCC(CC3)N4CCOCC4)C(C5=C(C2=O)C6=C(N5)C=C(C=C6)C#N)(C)C
InChI
1S/C30H34N4O2/c1-4-20-16-23-24(17-26(20)34-9-7-21(8-10-34)33-11-13-36-14-12-33)30(2,3)29-27(28(23)35)22-6-5-19(18-31)15-25(22)32-29/h5-6,15-17,21,32H,4,7-14H2,1-3H3
InChIKey
KDGFLJKFZUIJMX-UHFFFAOYSA-N
PubChem CID
49806720
ChEBI ID
CHEBI:90936
TTD Drug ID
D0U3SY
DrugBank ID
DB11363
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
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]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: ALK tyrosine kinase receptor (ALK) [1]
Resistant Disease Neuroblastoma [ICD-11: 2A00.11]
 Disease Info 
Molecule Alteration Missense mutation
p.F1174L
 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 Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
In Vitro Model NBLW cells Brain Homo sapiens (Human) CVCL_VJ90
NBLW-R cells Brain Homo sapiens (Human) CVCL_VJ91
Experiment for
Molecule Alteration		 Sangersequencing assay; Targeted deep sequencing assay
Experiment for
Drug Resistance		 Array CGH assay
Mechanism Description Analysis of the sensitivity of NBLW and NBLW-R cells to a panel of ALk inhibitors (TAE-684, Crizotinib, Alectinib and Lorlatinib) revealed differences between the paired cell lines, and overall NBLW-R cells with the F1174L mutation were more resistant to ALk inhibitor induced apoptosis compared with NBLW cells.
References
Ref 1 Identification of different ALK mutations in a pair of neuroblastoma cell lines established at diagnosis and relapse. Oncotarget. 2016 Dec 27;7(52):87301-87311. doi: 10.18632/oncotarget.13541.
Ref 2 Efficacy and Resistance of ALK Inhibitors in Two Inflammatory Myofibroblastic Tumor Patients with ALK Fusions Assessed by Whole Exome and RNA Sequencing .Onco Targets Ther. 2020 Oct 13;13:10335-10342. doi: 10.2147/OTT.S270481. eCollection 2020. 10.2147/OTT.S270481
Ref 3 Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96. doi: 10.1158/1078-0432.CCR-14-1511. Epub 2014 Sep 16.
Ref 4 Combined blockade of GPX4 and activated EGFR/HER3 bypass pathways inhibits the development of ALK-inhibitor-induced tolerant persister cells in ALK-fusion-positive lung cancer. Mol Oncol. 2025 Feb;19(2):519-539.
Ref 5 Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma .Mol Cancer Res. 2015 Apr;13(4):775-83. doi: 10.1158/1541-7786.MCR-14-0157. Epub 2014 Nov 24. 10.1158/1541-7786.MCR-14-0157

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