Drug Information

Drug (ID: DG01583) and It's Reported Resistant Information
Name
MK2206
Synonyms
1032350-13-2; MK-2206 dihydrochloride; MK-2206 2HCl; MK2206; UNII-Q34I3E28IO; 8-(4-(1-Aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one dihydrochloride; MK-2206 HCl salt; 8-[4-(1-AMINOCYCLOBUTYL)PHENYL]-9-PHENYL-1,2,4-TRIAZOLO[3,4-F][1,6]NAPHTHYRIDIN-3(2H)-ONE DIHYDROCHLORIDE; Q34I3E28IO; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one;dihydrochloride; C25H21N5O; MK 2206 2HCl; 1032349-77-1; MK 2206 dihydrochloride; C25H21N5O.HCl; C25H21N5O.2HCl; CHEMBL4635254; SCHEMBL17100521; EX-A259; SYN1162; AOB87741; MFCD14584463; s1078; AKOS015966903; CCG-264809; PB19401; 1,2,4-Triazolo(3,4-f)(1,6)naphthyridin-3(2H)-one, 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-, hydrochloride (1:2); 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one;dihydrochl; AC-28437; AS-16298; FT-0672430; SW202557-3; X7427; Z1978; P11738; J-000912; J-519356; Q27286944; (2R,4S)-4-[(3-Carboxy-1-oxopropyl)amino]-4-[(p-phenylphenyl)methyl]-2-methylbutanoic acid ethyl ester; 4-[[(2S,4R)-5-Ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid calcium salt; 4-{[(2S,4R)-1-(4-Biphenylyl)-5-ethoxy-4-methyl-5-oxo-2-pentanyl]amino}-4-oxobutanoic acid; 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl-1,2,4-triazolo[3,4-f][1,6]naphthyridin-3(2H)-one 2HCl; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H,3H-[1,2,4]triazolo[3,4-f]1,6-naphthyridin-3-one hydrochloride
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Indication
In total 2 Indication(s)
Nasopharyngeal carcinoma [ICD-11: 2B6B]
Phase 2
[1]
Rectal adenocarcinoma [ICD-11: 2B92]
Investigative
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Breast cancer [ICD-11: 2C60]
[2]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Target RAC-gamma serine/threonine-protein kinase (AKT3) AKT3_HUMAN [1]
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Formula
3
IsoSMILES
C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C4C(=N3)C=CN5C4=NNC5=O)C6=CC=CC=C6)N.Cl.Cl
InChI
InChI=1S/C25H21N5O.2ClH/c26-25(12-4-13-25)18-9-7-17(8-10-18)22-19(16-5-2-1-3-6-16)15-20-21(27-22)11-14-30-23(20)28-29-24(30)31;;/h1-3,5-11,14-15H,4,12-13,26H2,(H,29,31);2*1H
InChIKey
HWUHTJIKQZZBRA-UHFFFAOYSA-N
PubChem CID
46930998
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
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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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: RAC-alpha serine/threonine-protein kinase (AKT1) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.W80A (c.238_239delTGinsGC)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 3T3-L1 cells Nasopharynx Mus musculus (Mouse) CVCL_0123
Mechanism Description The missense mutation p.W80A (c.238_239delTGinsGC) in gene AKT1 cause the resistance of MK2206 by aberration of the drug's therapeutic target
Myeloproliferative neoplasm [ICD-11: 2A22]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Thrombopoietin receptor (TPOR) [3]
Sensitive Disease Myeloproliferative neoplasm [ICD-11: 2A22.0]
 Disease Info 
Molecule Alteration Missense mutation
p.W515L (c.1544G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model HEL cells Blood Homo sapiens (Human) CVCL_0001
SET2 cells Peripheral blood Homo sapiens (Human) CVCL_2187
In Vivo Model Balb/c donor mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 Trypan blue staining assay
Mechanism Description The missense mutation p.W515L (c.1544G>T) in gene MPL cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Breast cancer [ICD-11: 2C60]
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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: RAC-alpha serine/threonine-protein kinase (AKT1) [2]
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.W80A (c.238_239delTGinsGC)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model H1975 cells Lung Homo sapiens (Human) CVCL_1511
BT474 cells Breast Homo sapiens (Human) CVCL_0179
HCC827 cells Lung Homo sapiens (Human) CVCL_2063
MCF10A cells Breast Homo sapiens (Human) CVCL_0598
HCC4006 cells Lung Homo sapiens (Human) CVCL_1269
MDA-MB-361 cells Breast Homo sapiens (Human) CVCL_0620
GTL-16 cells Gastric Homo sapiens (Human) CVCL_7668
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
HCT116 cells Colon Homo sapiens (Human) CVCL_0291
MDA-MB-361 cells Breast Homo sapiens (Human) CVCL_0620
H1648 cells Lymph node Homo sapiens (Human) CVCL_1482
EBC1 cells Skin Homo sapiens (Human) CVCL_2891
Mechanism Description The missense mutation p.W80A (c.238_239delTGinsGC) in gene AKT1 cause the resistance of MK2206 by aberration of the drug's therapeutic target
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA) [4]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.H1047R (c.3140A>G)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 2.41  Å
PDB: 8DCP
Mutant Type Structure Method: X-ray diffraction Resolution: 2.61  Å
PDB: 8V8V
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.09
TM score: 0.95656
Amino acid change:
H1047R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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100
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110
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120
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140
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150
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180
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600
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610
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620
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630
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640
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650
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V
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660
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N
N
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670
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L
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N
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680
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690
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700
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710
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720
|
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730
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740
|
R
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750
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G
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760
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770
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R
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M
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A
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K
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780
|
W
W
L
L
N
N
W
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N
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P
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D
D
I
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M
M
790
|
S
S
E
E
L
L
L
L
F
F
Q
Q
N
N
N
N
E
E
I
I
800
|
I
I
F
F
K
K
N
N
G
G
D
D
D
D
L
L
R
R
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810
|
D
D
M
M
L
L
T
T
L
L
Q
Q
I
I
I
I
R
R
I
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820
|
M
M
E
E
N
N
I
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W
W
Q
Q
N
N
Q
Q
G
G
L
L
830
|
D
D
L
L
R
R
M
M
L
L
P
P
Y
Y
G
G
C
C
L
L
840
|
S
S
I
I
G
G
D
D
C
C
V
V
G
G
L
L
I
I
E
E
850
|
V
V
V
V
R
R
N
N
S
S
H
H
T
T
I
I
M
M
Q
Q
860
|
I
I
Q
Q
C
C
K
K
G
G
G
G
L
L
K
K
G
G
A
A
870
|
L
L
Q
Q
F
F
N
N
S
S
H
H
T
T
L
L
H
H
Q
Q
880
|
W
W
L
L
K
K
D
D
K
K
N
N
K
K
G
G
E
E
I
I
890
|
Y
Y
D
D
A
A
A
A
I
I
D
D
L
L
F
F
T
T
R
R
900
|
S
S
C
C
A
A
G
G
Y
Y
C
C
V
V
A
A
T
T
F
F
910
|
I
I
L
L
G
G
I
I
G
G
D
D
R
R
H
H
N
N
S
S
920
|
N
N
I
I
M
M
V
V
K
K
D
D
D
D
G
G
Q
Q
L
L
930
|
F
F
H
H
I
I
D
D
F
F
G
G
H
H
F
F
L
L
D
D
940
|
H
H
K
K
K
K
K
K
K
K
F
F
G
G
Y
Y
K
K
R
R
950
|
E
E
R
R
V
V
P
P
F
F
V
V
L
L
T
T
Q
Q
D
D
960
|
F
F
L
L
I
I
V
V
I
I
S
S
K
K
G
G
A
A
Q
Q
970
|
E
E
C
C
T
T
K
K
T
T
R
R
E
E
F
F
E
E
R
R
980
|
F
F
Q
Q
E
E
M
M
C
C
Y
Y
K
K
A
A
Y
Y
L
L
990
|
A
A
I
I
R
R
Q
Q
H
H
A
A
N
N
L
L
F
F
I
I
1000
|
N
N
L
L
F
F
S
S
M
M
M
M
L
L
G
G
S
S
G
G
1010
|
M
M
P
P
E
E
L
L
Q
Q
S
S
F
F
D
D
D
D
I
I
1020
|
A
A
Y
Y
I
I
R
R
K
K
T
T
L
L
A
A
L
L
D
D
1030
|
K
K
T
T
E
E
Q
Q
E
E
A
A
L
L
E
E
Y
Y
F
F
1040
|
M
M
K
K
Q
Q
M
M
N
N
D
D
A
A
H
R
H
H
G
G
1050
|
G
G
W
W
T
T
T
T
K
K
M
M
D
D
W
W
I
I
F
F
1060
|
H
H
T
T
I
I
K
K
Q
Q
H
H
A
A
L
L
N
N
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [4]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.H1047L (c.3140A>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.77  Å
PDB: 9ASF
Mutant Type Structure Method: X-ray diffraction Resolution: 1.96  Å
PDB: 7L1C
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.51
TM score: 0.61892
Amino acid change:
H1047L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
A
A
H
L
H
H
G
G
1050
|
G
G
-
W
T
T
T
T
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.H1047L (c.3140A>T) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [4]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.N345K (c.1035T>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.N345K (c.1035T>G) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [4]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.E542K (c.1624G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.E542K (c.1624G>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [4]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.E545K (c.1633G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [4]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.Q546K (c.1636C>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.Q546K (c.1636C>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [4]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G1049R (c.3145G>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF10A cells Breast Homo sapiens (Human) CVCL_0598
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
In Vivo Model Female nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunoblotting analysis
Mechanism Description The missense mutation p.G1049R (c.3145G>C) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Thyroid cancer [ICD-11: 2D10]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Nras (NRAS) [5]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q61R (c.182A>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.59  Å
PDB: 8TBI
Mutant Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 7F68
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.46
TM score: 0.94384
Amino acid change:
Q61R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
S
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
G
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
R
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
S
S
K
K
S
D
90
|
F
F
A
A
D
D
I
I
N
N
L
L
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
D
D
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
T
T
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
H
H
E
E
L
L
A
A
K
K
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
E
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
Q
Q
Y
Y
R
R
M
M
K
K
170
|
K
-
L
-
N
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.Q61R (c.182A>G) in gene NRAS cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: GTPase Hras (HRAS) [5]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G13R (c.37G>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.G13R (c.37G>C) in gene HRAS cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [5]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E545K (c.1633G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of MK2206 by unusual activation of pro-survival pathway
Key Molecule: Phosphatase and tensin homolog (PTEN) [5]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Nonsense
p.R130* (c.388C>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The nonsense p.R130* (c.388C>T) in gene PTEN cause the sensitivity of MK2206 by unusual activation of pro-survival pathway.
References
Ref 1 Development of a new model system to dissect isoform specific Akt signalling in adipocytesBiochem J. 2015 Jun 15;468(3):425-34. doi: 10.1042/BJ20150191. Epub 2015 Apr 9.
Ref 2 A kinase-independent function of AKT promotes cancer cell survivalElife. 2014 Dec 31;3:e03751. doi: 10.7554/eLife.03751.
Ref 3 AKT is a therapeutic target in myeloproliferative neoplasmsLeukemia. 2013 Sep;27(9):1882-90. doi: 10.1038/leu.2013.167. Epub 2013 Jun 10.
Ref 4 Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare MutationsCancer Res. 2015 Dec 15;75(24):5341-54. doi: 10.1158/0008-5472.CAN-15-1654. Epub 2015 Dec 1.
Ref 5 The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathwayJ Clin Endocrinol Metab. 2011 Apr;96(4):E577-85. doi: 10.1210/jc.2010-2644. Epub 2011 Feb 2.

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