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
    Click to Show/Hide
Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Structure
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]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
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
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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: Epidermal growth factor receptor (EGFR) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.N826S (c.2477A>G)
 Molecule Info 
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 blot 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]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L755S (c.2263_2264delCTinsAG)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L755P (c.2264T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.T798M (c.2393_2394delCAinsTG)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L858R (c.2573T>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.64  Å
PDB: 4LI5
Mutant Type Structure Method: X-ray diffraction Resolution: 2.47  Å
PDB: 2ITV
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.34
TM score: 0.90001
Amino acid change:
L858R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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870
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Click to Show/Hide the Structure
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 blot 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: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Complex-indel
p.L747_P753delinsS (c.2240_2257del18)
 Molecule Info 
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 blot 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: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V773A (c.2318T>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V777L (c.2329G>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.N857S (c.2570A>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.T862A (c.2584A>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.H878Y (c.2632C>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Western blot 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]
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: Epidermal growth factor receptor (EGFR) [2]
Resistant Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T790M (c.2369C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.10  Å
PDB: 2J6M
Mutant Type Structure Method: X-ray diffraction Resolution: 3.05  Å
PDB: 2JIU
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.57
TM score: 0.92063
Amino acid change:
T790M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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820
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870
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A
S
S
E
E
I
I
S
S
S
S
I
I
L
L
E
E
K
K
930
|
G
G
E
E
R
R
L
L
P
P
Q
Q
P
P
P
P
I
I
C
C
940
|
T
T
I
I
D
D
V
V
Y
Y
M
M
I
I
M
M
V
V
K
K
950
|
C
C
W
W
M
M
I
I
D
D
A
A
D
D
S
S
R
R
P
P
960
|
K
K
F
F
R
R
E
E
L
L
I
I
I
I
E
E
F
F
S
S
970
|
K
K
M
M
A
A
R
R
D
D
P
P
Q
Q
R
R
Y
Y
L
L
980
|
V
V
I
I
Q
Q
G
G
D
D
E
E
R
R
M
M
H
H
L
L
990
|
P
P
S
S
P
P
T
T
D
D
S
S
N
N
F
F
Y
Y
R
R
1000
|
A
A
L
L
M
M
D
D
E
E
E
E
D
D
M
M
D
D
D
D
1010
|
V
V
V
V
D
D
A
A
D
D
E
E
Y
Y
L
L
I
I
P
P
1020
|
Q
Q
Q
Q
G
G
Click to Show/Hide the Structure
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.

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