Drug Information

Drug (ID: DG00253) and It's Reported Resistant Information

• Name: NVP-TAE684
• Synonyms: 761439-42-3; NVP-TAE684; NVP-TAE 684; TAE684; TAE-684; 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidine-2,4-diamine; TAE684 (NVP-TAE684); TAE 684; UNII-EH1713MN4K; CHEMBL509032; EH1713MN4K; 5-Chloro-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-2,4-pyrimidinediamine; C30H40ClN7O3S
• Indication:
  In total 1 Indication(s)
  Lymphoma [ICD-11: 2A90- 2A85]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Brain cancer [ICD-11: 2A00]; [1]
• Target: Insulin receptor (INSR); INSR_HUMAN; [1]
• Formula: C30H40ClN7O3S
• IsoSMILES: CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC
• InChI: 1S/C30H40ClN7O3S/c1-21(2)42(39,40)28-8-6-5-7-26(28)33-29-24(31)20-32-30(35-29)34-25-10-9-23(19-27(25)41-4)37-13-11-22(12-14-37)38-17-15-36(3)16-18-38/h5-10,19-22H,11-18H2,1-4H3,(H2,32,33,34,35)
• InChIKey: QQWUGDVOUVUTOY-UHFFFAOYSA-N
• PubChem CID: 16038120
• ChEBI ID: CHEBI:91338
• TTD Drug ID: D0R2WK

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: ALK tyrosine kinase receptor (ALK) [1]

• Molecule Alteration: Missense mutation; p.F1174L
• Resistant Disease: Neuroblastoma [ICD-11: 2A00.11]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: NBLW cells; Brain; Homo sapiens (Human); CVCL_VJ90
• In Vitro Model: 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.