Drug Information

Drug (ID: DG01597) and It's Reported Resistant Information
Name
Miransertib
Synonyms
Miransertib; 1313881-70-7; ARQ-092; AKT inhibitor 2; ARQ 092 Free Base; ARQ092; ARQ 092; UNII-T1DQI1B52Y; T1DQI1B52Y; 3-[3-[4-(1-aminocyclobutyl)phenyl]-5-phenylimidazo[4,5-b]pyridin-2-yl]pyridin-2-amine; 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine; 3-[3-[4-(1-Azanylcyclobutyl)phenyl]-5-Phenyl-Imidazo[4,5-B]pyridin-2-Yl]pyridin-2-Amine; 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo(4,5-b)pyridin-2-yl)pyridin-2-amine; Miransertib [INN]; Miransertib [USAN]; Miransertib [WHO-DD]; Miransertib (USAN/INN); Miransertib [USAN:INN]; Miransertib (ARQ-092); GTPL9429; SCHEMBL2187875; CHEMBL4297188; BCP19821; EX-A1268; NSC791328; WHO 10490; ZINC72315647; CS-5377; DB14982; NSC-791328; SB19688; compound 21a [PMID: 27305487]; HY-19719; DB-105304; S6811; J3.532.768A; D11409; A922251; Q27456535; 2-Pyridinamine, 3-(3-(4-(1-aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo(4,5-b)pyridin-2-yl)-; 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo(4,5-b)pyridin-2-yl)-2-pyridinamine; 6S1
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Indication
In total 2 Indication(s)
Cholangiocarcinoma [ICD-11: 2C12]
Phase 2
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 2
[1]
Structure
Target Fibroblast growth factor receptor (FGFR) NOUNIPROTAC [2]
Fibroblast growth factor receptor 1 (FGFR1) FGFR1_HUMAN [2]
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Formula
4
IsoSMILES
C1CC(C1)(C2=CC=C(C=C2)N3C4=C(C=CC(=N4)C5=CC=CC=C5)N=C3C6=C(N=CC=C6)N)N
InChI
InChI=1S/C27H24N6/c28-24-21(8-4-17-30-24)25-32-23-14-13-22(18-6-2-1-3-7-18)31-26(23)33(25)20-11-9-19(10-12-20)27(29)15-5-16-27/h1-4,6-14,17H,5,15-16,29H2,(H2,28,30)
InChIKey
HNFMVVHMKGFCMB-UHFFFAOYSA-N
PubChem CID
53262401
TTD Drug ID
D03LWG
DrugBank ID
DB14982
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  RTDM: Regulation by the Disease Microenvironment
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
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Breast cancer [ICD-11: 2C60]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
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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M
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Y
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Y
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H
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H
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H
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-20
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H
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Y
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-10
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E
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-
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A
A
M
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0
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10
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20
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C
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L
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N
N
G
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30
|
M
M
I
I
V
V
T
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L
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40
|
A
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K
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H
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L
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50
|
F
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A
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L
L
H
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60
|
Q
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L
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D
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Y
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70
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F
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E
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A
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80
|
E
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F
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F
F
D
D
E
E
T
T
R
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R
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L
L
90
|
C
C
D
D
L
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L
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F
F
Q
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P
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F
F
L
L
100
|
K
K
V
V
I
I
E
E
P
P
V
V
G
G
N
N
R
R
E
E
110
|
E
E
K
K
I
I
L
L
N
N
R
R
E
E
I
I
G
G
F
F
120
|
A
A
I
I
G
G
M
M
P
P
V
V
C
C
E
E
F
F
D
D
130
|
M
M
V
V
K
K
D
D
P
P
E
E
V
V
Q
Q
D
D
F
F
140
|
R
R
R
R
N
N
I
I
L
L
N
N
V
V
C
C
K
K
E
E
150
|
A
A
V
V
D
D
L
L
R
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D
D
L
L
N
N
S
S
P
P
160
|
H
H
S
S
R
R
A
A
M
M
Y
Y
V
V
Y
Y
P
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170
|
N
N
V
V
E
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S
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P
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E
E
L
L
P
P
K
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180
|
H
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I
I
Y
Y
N
N
K
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L
L
D
D
K
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G
G
Q
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190
|
I
I
I
I
V
V
V
V
I
I
W
W
V
V
I
I
V
V
S
S
200
|
P
P
N
N
N
N
D
D
K
K
Q
Q
K
K
Y
Y
T
T
L
L
210
|
K
K
I
I
N
N
H
H
D
D
C
C
V
V
P
P
E
E
Q
Q
220
|
V
V
I
I
A
A
E
E
A
A
I
I
R
R
K
K
K
K
T
T
230
|
R
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S
S
M
M
L
L
L
L
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E
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Q
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L
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240
|
K
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L
L
C
C
V
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L
L
E
E
Y
Y
Q
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G
G
K
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250
|
Y
Y
I
I
L
L
K
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V
V
C
C
G
G
C
C
D
D
E
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260
|
Y
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L
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Y
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L
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270
|
Y
Y
K
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Y
Y
I
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R
S
S
C
C
I
I
M
M
L
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280
|
G
G
R
R
M
M
P
P
N
N
L
L
M
M
L
L
M
M
A
A
290
|
K
K
E
E
S
S
L
L
Y
Y
S
S
Q
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L
L
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M
M
300
|
D
D
C
C
F
F
T
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M
M
P
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S
S
Y
Y
S
S
R
R
310
|
R
R
I
I
S
S
T
T
A
A
T
T
P
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Y
Y
M
M
N
N
320
|
G
G
E
E
T
T
S
S
T
T
K
K
S
S
L
L
W
W
V
V
330
|
I
I
N
N
S
S
A
A
L
L
R
R
I
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K
K
I
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L
L
340
|
C
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A
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T
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Y
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V
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N
N
V
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N
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I
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350
|
D
D
I
I
D
D
K
K
I
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Y
Y
V
V
R
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T
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G
G
360
|
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Y
Y
H
H
G
G
G
G
E
E
P
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L
L
C
C
D
D
370
|
N
N
V
V
N
N
T
T
Q
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R
V
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P
P
C
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380
|
N
N
P
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W
W
N
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E
E
W
W
L
L
N
N
Y
Y
390
|
D
D
I
I
Y
Y
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D
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A
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400
|
A
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L
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C
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C
C
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410
|
K
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G
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A
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E
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420
|
C
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G
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N
N
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N
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L
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430
|
F
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D
Y
Y
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G
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440
|
K
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M
M
A
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L
L
N
N
L
L
W
W
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P
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450
|
H
H
G
G
L
L
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L
L
L
L
N
N
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I
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460
|
G
G
V
V
T
T
G
G
S
S
N
N
P
P
N
N
K
K
E
E
470
|
T
T
P
P
C
C
L
L
E
E
L
L
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E
F
F
D
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W
W
480
|
F
F
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S
S
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V
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M
M
490
|
S
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V
V
I
I
E
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A
A
N
N
W
W
S
S
500
|
V
V
S
S
R
R
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A
A
G
G
F
F
S
S
Y
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S
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510
|
H
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A
A
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G
L
L
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N
N
R
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L
L
A
A
R
R
520
|
D
D
N
N
E
E
L
L
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R
E
E
N
N
D
D
K
K
E
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530
|
Q
Q
L
L
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K
A
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540
|
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E
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550
|
F
F
L
L
W
W
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H
H
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R
H
H
Y
Y
C
C
V
V
560
|
T
T
I
I
P
P
E
E
I
I
L
L
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P
K
K
L
L
L
L
570
|
L
L
S
S
V
V
K
K
W
W
N
N
S
S
R
R
D
D
E
E
580
|
V
V
A
A
Q
Q
M
M
Y
Y
C
C
L
L
V
V
K
K
D
D
590
|
W
W
P
P
P
P
I
I
K
K
P
P
E
E
Q
Q
A
A
M
M
600
|
E
E
L
L
L
L
D
D
C
C
N
N
Y
Y
P
P
D
D
P
P
610
|
M
M
V
V
R
R
G
G
F
F
A
A
V
V
R
R
C
C
L
L
620
|
E
E
K
K
Y
Y
L
L
T
T
D
D
D
D
K
K
L
L
S
S
630
|
Q
Q
Y
Y
L
L
I
I
Q
Q
L
L
V
V
Q
Q
V
V
L
L
640
|
K
K
Y
Y
E
E
Q
Q
Y
Y
L
L
D
D
N
N
L
L
L
L
650
|
V
V
R
R
F
F
L
L
L
L
K
K
K
K
A
A
L
L
T
T
660
|
N
N
Q
Q
R
R
I
I
G
G
H
H
F
F
F
F
F
F
W
W
670
|
H
H
L
L
K
K
S
S
E
E
M
M
H
H
N
N
K
K
T
T
680
|
V
V
S
S
Q
Q
R
R
F
F
G
G
L
L
L
L
L
L
E
E
690
|
S
S
Y
Y
C
C
R
R
A
A
C
C
G
G
M
M
Y
Y
L
L
700
|
K
K
H
H
L
L
N
N
R
R
Q
Q
V
V
E
E
A
A
M
M
710
|
E
E
K
K
L
L
I
I
N
N
L
L
T
T
D
D
I
I
L
L
720
|
K
K
Q
Q
E
E
K
K
K
K
D
D
E
E
T
T
Q
Q
K
K
730
|
V
V
Q
Q
M
M
K
K
F
F
L
L
V
V
E
E
Q
Q
M
M
740
|
R
R
R
R
P
P
D
D
F
F
M
M
D
D
A
A
L
L
Q
Q
750
|
G
G
F
F
L
L
S
S
P
P
L
L
N
N
P
P
A
A
H
H
760
|
Q
Q
L
L
G
G
N
N
L
L
R
R
L
L
E
E
E
E
C
C
770
|
R
R
I
I
M
M
S
S
S
S
A
A
K
K
R
R
P
P
L
L
780
|
W
W
L
L
N
N
W
W
E
E
N
N
P
P
D
D
I
I
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
Q
Q
810
|
D
D
M
M
L
L
T
T
L
L
Q
Q
I
I
I
I
R
R
I
I
820
|
M
M
E
E
N
N
I
I
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 DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Mechanism Description The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of Miransertib by aberration of the drug's therapeutic target
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
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 DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Mechanism Description The missense mutation p.E542K (c.1624G>A) in gene PIK3CA cause the sensitivity of Miransertib by aberration of the drug's therapeutic target
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
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 DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Mechanism Description The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of Miransertib by aberration of the drug's therapeutic target
Ovarian cancer [ICD-11: 2C73]
Click to Show/Hide
Drug Sensitivity 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]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 1UNP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.94  Å
PDB: 2UZR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.26
TM score: 0.99569
Amino acid change:
E17K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
-
S
M
M
S
S
D
D
V
V
A
A
I
I
V
V
K
K
E
E
10
|
G
G
W
W
L
L
H
H
K
K
R
R
G
G
E
K
Y
Y
I
I
20
|
K
K
T
T
W
W
R
R
P
P
R
R
Y
Y
F
F
L
L
L
L
30
|
K
K
N
N
D
D
G
G
T
T
F
F
I
I
G
G
Y
Y
K
K
40
|
E
E
R
R
P
P
Q
Q
D
D
V
V
D
D
Q
Q
R
R
E
E
50
|
A
A
P
P
L
L
N
N
N
N
F
F
S
S
V
V
A
A
Q
Q
60
|
C
C
Q
Q
L
L
M
M
K
K
T
T
E
E
R
R
P
P
R
R
70
|
P
P
N
N
T
T
F
F
I
I
I
I
R
R
C
C
L
L
Q
Q
80
|
W
W
T
T
T
T
V
V
I
I
E
E
R
R
T
T
F
F
H
H
90
|
V
V
E
E
T
T
P
P
E
E
E
E
R
R
E
E
E
E
W
W
100
|
T
T
T
T
A
A
I
I
Q
Q
T
T
V
V
A
A
D
D
G
G
110
|
L
L
K
K
K
K
Q
Q
E
E
E
E
E
E
E
E
M
M
D
D
120
|
F
F
R
R
-
S
-
G
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Miransertib by aberration of the drug's therapeutic target
Endometrial cancer [ICD-11: 2C76]
Click to Show/Hide
Drug Sensitivity 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]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 1UNP
Mutant Type Structure Method: X-ray diffraction Resolution: 1.94  Å
PDB: 2UZR
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.26
TM score: 0.99569
Amino acid change:
E17K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
-
S
M
M
S
S
D
D
V
V
A
A
I
I
V
V
K
K
E
E
10
|
G
G
W
W
L
L
H
H
K
K
R
R
G
G
E
K
Y
Y
I
I
20
|
K
K
T
T
W
W
R
R
P
P
R
R
Y
Y
F
F
L
L
L
L
30
|
K
K
N
N
D
D
G
G
T
T
F
F
I
I
G
G
Y
Y
K
K
40
|
E
E
R
R
P
P
Q
Q
D
D
V
V
D
D
Q
Q
R
R
E
E
50
|
A
A
P
P
L
L
N
N
N
N
F
F
S
S
V
V
A
A
Q
Q
60
|
C
C
Q
Q
L
L
M
M
K
K
T
T
E
E
R
R
P
P
R
R
70
|
P
P
N
N
T
T
F
F
I
I
I
I
R
R
C
C
L
L
Q
Q
80
|
W
W
T
T
T
T
V
V
I
I
E
E
R
R
T
T
F
F
H
H
90
|
V
V
E
E
T
T
P
P
E
E
E
E
R
R
E
E
E
E
W
W
100
|
T
T
T
T
A
A
I
I
Q
Q
T
T
V
V
A
A
D
D
G
G
110
|
L
L
K
K
K
K
Q
Q
E
E
E
E
E
E
E
E
M
M
D
D
120
|
F
F
R
R
-
S
-
G
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Miransertib by aberration of the drug's therapeutic target
References
Ref 1 Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092PLoS One. 2015 Oct 15;10(10):e0140479. doi: 10.1371/journal.pone.0140479. eCollection 2015.
Ref 2 First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinomaAm J Med Genet A. 2019 Jul;179(7):1319-1324. doi: 10.1002/ajmg.a.61160. Epub 2019 May 6.

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