Molecule Information

General Information of the Molecule (ID: Mol00372)
Name
Fibroblast growth factor receptor 2 (FGFR2) ,Homo sapiens
Molecule Type
Protein
Gene Name
FGFR2
Gene ID
2263
Location
chr10:121478332-121598458[-]
Sequence
MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGESLEV
RCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETWYF
MVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCP
AGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSI
NHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSK
YGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVL
PAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTK
RIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDK
LTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKM
IGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARRPPGMEYSYDINRVPEEQMTF
KDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKT
TNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGH
RMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYS
PSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT
    Click to Show/Hide
3D-structure
PDB ID
2PSQ
Classification
Transferase
Method
X-ray diffraction
Resolution
2.40  Å
Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.
    Click to Show/Hide
Uniprot ID
FGFR2_HUMAN
Ensembl ID
ENSG00000066468
HGNC ID
HGNC:3689
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule with Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Infigratinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Infigratinib
 Drug Info 
Molecule Alteration Missense mutation
p.V564F (c.1690G>T)
Wild Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 2PSQ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.22  Å
PDB: 7KIA
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.64
TM score: 0.98452
Amino acid change:
V564F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
400
|
G
-
S
-
S
-
H
-
H
-
H
-
H
-
H
-
H
-
S
-
410
|
Q
-
D
-
P
-
P
-
A
-
V
-
H
-
K
-
L
-
T
-
420
|
K
-
R
-
I
-
P
-
L
-
R
-
R
-
Q
-
V
-
T
-
430
|
V
-
S
-
A
-
E
-
S
-
S
-
S
-
S
-
M
-
N
-
440
|
S
-
N
-
T
-
P
-
L
-
V
-
R
-
I
-
T
-
T
-
450
|
R
-
L
-
S
-
S
-
T
-
A
-
D
-
T
-
P
-
M
-
460
|
L
-
A
A
G
G
V
V
S
S
E
E
Y
Y
E
E
L
L
P
P
470
|
E
E
D
D
P
P
K
K
W
W
E
E
F
F
P
P
R
R
D
D
480
|
K
K
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
E
E
490
|
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
E
E
500
|
A
A
V
V
G
G
I
I
D
D
K
K
D
D
K
K
P
P
K
K
510
|
E
E
A
A
V
V
T
T
V
V
A
A
V
V
K
K
M
M
L
L
520
|
K
K
D
D
D
D
A
A
T
T
E
E
K
K
D
D
L
L
S
S
530
|
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
K
K
540
|
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
N
N
550
|
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
D
D
G
G
P
P
560
|
L
L
Y
Y
V
V
I
I
V
F
E
E
Y
Y
A
A
S
S
K
K
570
|
G
G
N
N
L
L
R
R
E
E
Y
Y
L
L
R
R
A
A
R
R
580
|
R
R
P
P
P
P
G
G
M
M
E
E
Y
Y
S
S
Y
Y
D
D
590
|
I
I
N
N
R
R
V
V
P
P
E
E
E
E
Q
Q
M
M
T
T
600
|
F
F
K
K
D
D
L
L
V
V
S
S
C
C
T
T
Y
Y
Q
Q
610
|
L
L
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
S
S
620
|
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
A
A
630
|
R
R
N
N
V
V
L
L
V
V
T
T
E
E
N
N
N
N
V
V
640
|
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
R
R
650
|
D
D
I
I
N
N
N
N
I
I
D
D
Y
Y
Y
Y
K
K
K
K
660
|
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
W
W
670
|
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
V
V
680
|
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
F
F
690
|
G
G
V
V
L
L
M
M
W
W
E
E
I
I
F
F
T
T
L
L
700
|
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
V
V
710
|
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
G
G
720
|
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
T
T
730
|
N
N
E
E
L
L
Y
Y
M
M
M
M
M
M
R
R
D
D
C
C
740
|
W
W
H
H
A
A
V
V
P
P
S
S
Q
Q
R
R
P
P
T
T
750
|
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
R
R
760
|
I
I
L
L
T
T
L
L
T
T
T
T
N
N
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Gallbladder N.A.
Experiment for
Molecule Alteration		 Targeted sequencing of tumor tissue assay
Mechanism Description The missense mutation p.V564F (c.1690G>T) in gene FGFR2 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Clinical Trial Drug(s)
7 drug(s) in total
Click to Show/Hide the Full List of Drugs
Brivanib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [2]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Sensitive Drug Brivanib
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Brivanib by unusual activation of pro-survival pathway
Cediranib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [2]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Sensitive Drug Cediranib
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway
Derazantinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [3]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Sensitive Drug Derazantinib
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation FGF/FGFR signaling pathway Inhibition hsa01521
In Vitro Model A2780 cells Ovary Homo sapiens (Human) CVCL_0134
KG-1 cells Bone marrow Homo sapiens (Human) CVCL_0374
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
AN3CA cells Ovary Homo sapiens (Human) CVCL_0028
SkOV3 cells Ovary Homo sapiens (Human) CVCL_0532
K562 cells Blood Homo sapiens (Human) CVCL_0004
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
RT-112 cells Urinary bladder Homo sapiens (Human) CVCL_1670
MFM-223 cells Pleural effusion Homo sapiens (Human) CVCL_1408
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
COS-1 cells Kidney Chlorocebus aethiops (Green monkey) CVCL_0223
In Vivo Model SCID beige mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2alpha, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions.
Selumetinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [4]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Resistant Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
SUM-52PE cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
KMS-11 cells Pleural effusion Homo sapiens (Human) CVCL_2989
HSC-39 cells Ascites Homo sapiens (Human) CVCL_A385
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
KATO-III cells Pleural effusion Homo sapiens (Human) CVCL_0371
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
Experiment for
Molecule Alteration		 Microarray assay; Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
AZD-4547
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [5]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AZD-4547
 Drug Info 
Molecule Alteration Missense mutation
p.V564F (c.1690G>T)
Wild Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 2PSQ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.22  Å
PDB: 7KIA
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.64
TM score: 0.98452
Amino acid change:
V564F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
400
|
G
-
S
-
S
-
H
-
H
-
H
-
H
-
H
-
H
-
S
-
410
|
Q
-
D
-
P
-
P
-
A
-
V
-
H
-
K
-
L
-
T
-
420
|
K
-
R
-
I
-
P
-
L
-
R
-
R
-
Q
-
V
-
T
-
430
|
V
-
S
-
A
-
E
-
S
-
S
-
S
-
S
-
M
-
N
-
440
|
S
-
N
-
T
-
P
-
L
-
V
-
R
-
I
-
T
-
T
-
450
|
R
-
L
-
S
-
S
-
T
-
A
-
D
-
T
-
P
-
M
-
460
|
L
-
A
A
G
G
V
V
S
S
E
E
Y
Y
E
E
L
L
P
P
470
|
E
E
D
D
P
P
K
K
W
W
E
E
F
F
P
P
R
R
D
D
480
|
K
K
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
E
E
490
|
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
E
E
500
|
A
A
V
V
G
G
I
I
D
D
K
K
D
D
K
K
P
P
K
K
510
|
E
E
A
A
V
V
T
T
V
V
A
A
V
V
K
K
M
M
L
L
520
|
K
K
D
D
D
D
A
A
T
T
E
E
K
K
D
D
L
L
S
S
530
|
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
K
K
540
|
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
N
N
550
|
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
D
D
G
G
P
P
560
|
L
L
Y
Y
V
V
I
I
V
F
E
E
Y
Y
A
A
S
S
K
K
570
|
G
G
N
N
L
L
R
R
E
E
Y
Y
L
L
R
R
A
A
R
R
580
|
R
R
P
P
P
P
G
G
M
M
E
E
Y
Y
S
S
Y
Y
D
D
590
|
I
I
N
N
R
R
V
V
P
P
E
E
E
E
Q
Q
M
M
T
T
600
|
F
F
K
K
D
D
L
L
V
V
S
S
C
C
T
T
Y
Y
Q
Q
610
|
L
L
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
S
S
620
|
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
A
A
630
|
R
R
N
N
V
V
L
L
V
V
T
T
E
E
N
N
N
N
V
V
640
|
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
R
R
650
|
D
D
I
I
N
N
N
N
I
I
D
D
Y
Y
Y
Y
K
K
K
K
660
|
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
W
W
670
|
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
V
V
680
|
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
F
F
690
|
G
G
V
V
L
L
M
M
W
W
E
E
I
I
F
F
T
T
L
L
700
|
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
V
V
710
|
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
G
G
720
|
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
T
T
730
|
N
N
E
E
L
L
Y
Y
M
M
M
M
M
M
R
R
D
D
C
C
740
|
W
W
H
H
A
A
V
V
P
P
S
S
Q
Q
R
R
P
P
T
T
750
|
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
R
R
760
|
I
I
L
L
T
T
L
L
T
T
T
T
N
N
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [6]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Resistant Drug AZD-4547
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
MOLM-1 cells Bone marrow Homo sapiens (Human) CVCL_2188
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
In Vivo Model Female balb/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Phospho-kinase array analysis; Reporter gene assay; Microarray analysis; RT-PCR; Gene set enrichment analysis
Experiment for
Drug Resistance		 MTT assay; Soft-agar colony assay
DEBIO-1347
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [5]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Sensitive Drug DEBIO-1347
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [5]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug DEBIO-1347
 Drug Info 
Molecule Alteration Missense mutation
p.V564F (c.1690G>T)
Wild Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 2PSQ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.22  Å
PDB: 7KIA
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.64
TM score: 0.98452
Amino acid change:
V564F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
400
|
G
-
S
-
S
-
H
-
H
-
H
-
H
-
H
-
H
-
S
-
410
|
Q
-
D
-
P
-
P
-
A
-
V
-
H
-
K
-
L
-
T
-
420
|
K
-
R
-
I
-
P
-
L
-
R
-
R
-
Q
-
V
-
T
-
430
|
V
-
S
-
A
-
E
-
S
-
S
-
S
-
S
-
M
-
N
-
440
|
S
-
N
-
T
-
P
-
L
-
V
-
R
-
I
-
T
-
T
-
450
|
R
-
L
-
S
-
S
-
T
-
A
-
D
-
T
-
P
-
M
-
460
|
L
-
A
A
G
G
V
V
S
S
E
E
Y
Y
E
E
L
L
P
P
470
|
E
E
D
D
P
P
K
K
W
W
E
E
F
F
P
P
R
R
D
D
480
|
K
K
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
E
E
490
|
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
E
E
500
|
A
A
V
V
G
G
I
I
D
D
K
K
D
D
K
K
P
P
K
K
510
|
E
E
A
A
V
V
T
T
V
V
A
A
V
V
K
K
M
M
L
L
520
|
K
K
D
D
D
D
A
A
T
T
E
E
K
K
D
D
L
L
S
S
530
|
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
K
K
540
|
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
N
N
550
|
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
D
D
G
G
P
P
560
|
L
L
Y
Y
V
V
I
I
V
F
E
E
Y
Y
A
A
S
S
K
K
570
|
G
G
N
N
L
L
R
R
E
E
Y
Y
L
L
R
R
A
A
R
R
580
|
R
R
P
P
P
P
G
G
M
M
E
E
Y
Y
S
S
Y
Y
D
D
590
|
I
I
N
N
R
R
V
V
P
P
E
E
E
E
Q
Q
M
M
T
T
600
|
F
F
K
K
D
D
L
L
V
V
S
S
C
C
T
T
Y
Y
Q
Q
610
|
L
L
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
S
S
620
|
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
A
A
630
|
R
R
N
N
V
V
L
L
V
V
T
T
E
E
N
N
N
N
V
V
640
|
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
R
R
650
|
D
D
I
I
N
N
N
N
I
I
D
D
Y
Y
Y
Y
K
K
K
K
660
|
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
W
W
670
|
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
V
V
680
|
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
F
F
690
|
G
G
V
V
L
L
M
M
W
W
E
E
I
I
F
F
T
T
L
L
700
|
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
V
V
710
|
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
G
G
720
|
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
T
T
730
|
N
N
E
E
L
L
Y
Y
M
M
M
M
M
M
R
R
D
D
C
C
740
|
W
W
H
H
A
A
V
V
P
P
S
S
Q
Q
R
R
P
P
T
T
750
|
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
R
R
760
|
I
I
L
L
T
T
L
L
T
T
T
T
N
N
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. N.A. N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
RO-5126766 free base
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [4]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Sensitive Drug RO-5126766 free base
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
SUM-52PE cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
KMS-11 cells Pleural effusion Homo sapiens (Human) CVCL_2989
HSC-39 cells Ascites Homo sapiens (Human) CVCL_A385
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
KATO-III cells Pleural effusion Homo sapiens (Human) CVCL_0371
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
Experiment for
Molecule Alteration		 Microarray assay; Western blot analysis
Experiment for
Drug Resistance		 CCK-8 assay
Preclinical Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
E7090
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [7]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Sensitive Drug E7090
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
GSK3052230
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Endometrial adenocarcinoma [ICD-11: 2C76.0] [8]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Sensitive Drug GSK3052230
 Drug Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
Wild Type Structure Method: X-ray diffraction Resolution: 3.88  Å
PDB: 4J23
Mutant Type Structure Method: X-ray diffraction Resolution: 2.70  Å
PDB: 1II4
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.81
TM score: 0.89346
Amino acid change:
S252W
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
-
N
N
S
S
N
N
150
|
N
N
K
K
R
R
A
A
P
P
Y
Y
W
W
T
T
N
N
T
T
160
|
E
E
K
K
M
M
E
E
K
K
R
R
L
L
H
H
A
A
V
V
170
|
P
P
A
A
A
A
N
N
T
T
V
V
K
K
F
F
R
R
C
C
180
|
P
P
A
A
G
G
G
G
N
N
P
P
M
M
P
P
T
T
M
M
190
|
R
R
W
W
L
L
K
K
N
N
G
G
K
K
E
E
F
F
K
K
200
|
Q
Q
E
E
H
H
R
R
I
I
G
G
G
G
Y
Y
K
K
V
V
210
|
R
R
N
N
Q
Q
H
H
W
W
S
S
L
L
I
I
M
M
E
E
220
|
S
S
V
V
V
V
P
P
S
S
D
D
K
K
G
G
N
N
Y
Y
230
|
T
T
C
C
V
V
V
V
E
E
N
N
E
E
Y
Y
G
G
S
S
240
|
I
I
N
N
H
H
T
T
Y
Y
H
H
L
L
D
D
V
V
V
V
250
|
E
E
R
R
S
W
P
P
H
H
R
R
P
P
I
I
L
L
Q
Q
260
|
A
A
G
G
L
L
P
P
A
A
N
N
A
A
S
S
T
T
V
V
270
|
V
V
G
G
G
G
D
D
V
V
E
E
F
F
V
V
C
C
K
K
280
|
V
V
Y
Y
S
S
D
D
A
A
Q
Q
P
P
H
H
I
I
Q
Q
290
|
W
W
I
I
K
K
H
H
V
V
E
E
K
K
N
N
G
G
S
S
300
|
K
K
Y
Y
G
G
P
P
D
D
G
G
L
L
P
P
Y
Y
L
L
310
|
K
K
V
V
L
L
K
K
A
A
A
A
G
G
V
V
N
N
T
T
320
|
T
T
D
D
K
K
E
E
I
I
E
E
V
V
L
L
Y
Y
I
I
330
|
R
R
N
N
V
V
T
T
F
F
E
E
D
D
A
A
G
G
E
E
340
|
Y
Y
T
T
C
C
L
L
A
A
G
G
N
N
S
S
I
I
G
G
350
|
I
I
S
S
F
F
H
H
S
S
A
A
W
W
L
L
T
T
V
V
360
|
L
L
P
P
A
A
P
P
G
G
R
R
E
E
L
-
E
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Lung N.A.
Experiment for
Molecule Alteration		 QuantiGene Plex DNA assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of GSK3052230 by aberration of the drug's therapeutic target
References
Ref 1 Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive CholangiocarcinomaCancer Discov. 2017 Mar;7(3):252-263. doi: 10.1158/2159-8290.CD-16-1000. Epub 2016 Dec 29.
Ref 2 Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer modelsMol Cancer Ther. 2012 Mar;11(3):690-9. doi: 10.1158/1535-7163.MCT-11-0450. Epub 2012 Jan 11.
Ref 3 Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR DysregulationPLoS One. 2016 Sep 14;11(9):e0162594. doi: 10.1371/journal.pone.0162594. eCollection 2016.
Ref 4 ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR InhibitorMol Cancer Ther. 2015 Dec;14(12):2831-9. doi: 10.1158/1535-7163.MCT-15-0497. Epub 2015 Oct 5.
Ref 5 The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitorMol Cancer Ther. 2014 Nov;13(11):2547-58. doi: 10.1158/1535-7163.MCT-14-0248. Epub 2014 Aug 28.
Ref 6 Antitumor Effects and Mechanisms of AZD4547 on FGFR2-Deregulated Endometrial Cancer CellsMol Cancer Ther. 2015 Oct;14(10):2292-302. doi: 10.1158/1535-7163.MCT-15-0032. Epub 2015 Aug 20.
Ref 7 E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical ModelsMol Cancer Ther. 2016 Nov;15(11):2630-2639. doi: 10.1158/1535-7163.MCT-16-0261. Epub 2016 Aug 17.
Ref 8 Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancerSci Transl Med. 2013 Mar 27;5(178):178ra39. doi: 10.1126/scitranslmed.3005414.

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