Drug Information

Drug (ID: DG01509) and It's Reported Resistant Information

• Name: AEE-788
• Synonyms: 497839-62-0; AEE788; AEE-788; AEE 788; NVP-AEE788; (R)-6-(4-((4-Ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; AEE788 (NVP-AEE788); UNII-F9JLR95I3I; GNF-Pf-5343; F9JLR95I3I; NVP-AEE-788; 6-{4-[(4-Ethylpiperazin-1-Yl)methyl]phenyl}-N-[(1r)-1-Phenylethyl]-7h-Pyrrolo[2,3-D]pyrimidin-4-Amine; 6-[4-[(4-Ethyl-1-piperazinyl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine; C27H32N6; (R)-6-(4-((4-ethylpiperazin-1-yl)methyl)phenyl)-N-(1-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine.; 7H-Pyrrolo[2,3-d]pyrimidin-4-amine,6-[4-[(4-ethyl-1-piperazinyl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-; 6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine; 7h-pyrrolo[2,3-d]pyrimidin-4-amine,6-(4-((4-ethyl-1-piperazinyl)methyl)phenyl)-n-((1r)-1-phenylethyl)-; AEE; MLS006011277; SCHEMBL613756; CHEMBL587723; GTPL7643; BDBM26105; CHEBI:40629; AEE788; NVP-AEE788; BCPP000427; EX-A2259; MFCD11100351; NSC765949; NSC799325; s1486; ZINC22453679; AEE-788 (NVP-AEE788); AKOS016011091; BCP9000241; CCG-264897; CS-1452; DB12558; NSC-765949; NSC-799325; QC-8215; NCGC00263149-01; 7H-pyrrolo(2,3-d)pyrimidin-4-amine, 6-(4-((4-ethyl-1-piperazinyl)methyl)phenyl)-N-((1R)-1-phenylethyl)-; AC-32829; AEE788, >=98% (HPLC); AS-55853; HY-10045; SMR004703027; SW219869-1; X7492; J-518187; Q4651286; UNII-F9JLR95I3I component OONFNUWBHFSNBT-HXUWFJFHSA-N; [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-((r)-1-phenylethyl)amine; 1H-Pyrrolo(2,3-d)pyrimidin-4-amine, 6-(4-((4-ethyl-1-piperazinyl)methyl)phenyl)-N-((1R)-1-phenylethyl)-; 6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[3,2-e]pyrimidin-4-amine; 6-{4-[(4-ethyl-1-piperazinyl)methyl]phenyl}-N-[(1R)-1-phenylethyl]-1H-pyrrolo[2,3-d]pyrimidin-4-amine; NVP-AEE788; ; ; 6-[4-[(4-Ethylpiperazin-1-yl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Lung cancer [ICD-11: 2C25]; [2]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [1]
• Target: Fibroblast growth factor receptor 2 (FGFR2); FGFR2_HUMAN; [1]
• Formula: 7
• IsoSMILES: CCN1CCN(CC1)CC2=CC=C(C=C2)C3=CC4=C(N3)N=CN=C4N[C@H](C)C5=CC=CC=C5
• InChI: InChI=1S/C27H32N6/c1-3-32-13-15-33(16-14-32)18-21-9-11-23(12-10-21)25-17-24-26(28-19-29-27(24)31-25)30-20(2)22-7-5-4-6-8-22/h4-12,17,19-20H,3,13-16,18H2,1-2H3,(H2,28,29,30,31)/t20-/m1/s1
• InChIKey: OONFNUWBHFSNBT-HXUWFJFHSA-N
• PubChem CID: 10297043
• DrugBank ID: DB12558

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.N826S (c.2477A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter96 Proliferation assay
• Mechanism Description: The missense mutation p.N826S (c.2477A>G) in gene EGFR cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.L755S (c.2263_2264delCTinsAG)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.L755P (c.2264T>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.T798M (c.2393_2394delCAinsTG)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the resistance of AEE-788 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Complex-indel; p.L747_P753delinsS (c.2240_2257del18)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter96 Proliferation assay
• Mechanism Description: The complex-indel p.L747_P753delinsS (c.2240_2257del18) in gene EGFR cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target.

Key Molecule: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter96 Proliferation assay
• Mechanism Description: The missense mutation p.L858R (c.2573T>G) in gene EGFR cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.V773A (c.2318T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.V773A (c.2318T>C) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.V777L (c.2329G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.V777L (c.2329G>C) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.N857S (c.2570A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.N857S (c.2570A>G) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.T862A (c.2584A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.T862A (c.2584A>G) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Missense mutation; p.H878Y (c.2632C>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.H878Y (c.2632C>T) in gene ERBB2 cause the sensitivity of AEE-788 by aberration of the drug's therapeutic target

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [2]

• Molecule Alteration: Missense mutation; p.T790M (c.2369C>T)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: Enzyme kinetic assays
• Mechanism Description: The missense mutation p.T790M (c.2369C>T) in gene EGFR cause the resistance of AEE-788 by aberration of the drug's therapeutic target

References

• Ref 1: Functional analysis of epidermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapyClin Cancer Res. 2009 Jan 15;15(2):460-7. doi: 10.1158/1078-0432.CCR-08-1757.
• Ref 2: The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATPProc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5. doi: 10.1073/pnas.0709662105. Epub 2008 Jan 28.
• Ref 3: Differential sensitivity of ERBB2 kinase domain mutations towards lapatinibPLoS One. 2011;6(10):e26760. doi: 10.1371/journal.pone.0026760. Epub 2011 Oct 28.