Molecule Information

General Information of the Molecule (ID: Mol01836)
Name
Fibroblast growth factor receptor 3 (FGFR3) ,Homo sapiens
Synonyms
Fibroblast growth factor receptor 3; FGFR-3; CD antigen CD333; JTK4
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Molecule Type
Protein
Gene Name
FGFR3
Gene ID
2261
Location
chr4:1,793,293-1,808,872[+]
Sequence
MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELS
CPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLTQRVLCH
FSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAG
NPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQT
YTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGP
DGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAE
EELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCRLRSPPKKGLGSPTVHKISRFPLK
RQVSLESNASMSSNTPLVRIARLSSGEGPTLANVSELELPADPKWELSRARLTLGKPLGE
GCFGQVVMAEAIGIDKDRAAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIIN
LLGACTQGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSCAYQ
VARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNLDYYKKTTNGRLPVKW
MAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCT
HDLYMIMRECWHAAPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSS
SSSGDDSVFAHDLLPPAPPSSGGSRT
    Click to Show/Hide
3D-structure
PDB ID
1RY7
Classification
Growth factor/growth factor receptor
Method
X-ray diffraction
Resolution
3.20  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 and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. 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. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling.
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Uniprot ID
FGFR3_HUMAN
Ensembl ID
ENSG00000068078
HGNC ID
HGNC:3690
        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)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
Erdafitinib
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: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug Erdafitinib
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
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G
-
S
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S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
E
E
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH3T3 cells Embryo Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 Promega assay
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] [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Infigratinib
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
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.K650E (c.1948A>G) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug Infigratinib
 Drug Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
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.V555M (c.1663G>A) in gene FGFR3 cause the resistance of Infigratinib by aberration of the drug's therapeutic target
Disease Class: Transitional cell carcinoma [ICD-11: 2C9Z.0] [3]
Resistant Disease Transitional cell carcinoma [ICD-11: 2C9Z.0]
 Disease Info 
Resistant Drug Infigratinib
 Drug Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Clinical Trial Drug(s)
3 drug(s) in total
Click to Show/Hide the Full List of Drugs
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] [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AZD-4547
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
E
E
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH3T3 cells Embryo Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 Promega assay
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug AZD-4547
 Drug Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
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.V555M (c.1663G>A) in gene FGFR3 cause the resistance of AZD-4547 by aberration of the drug's therapeutic target
DEBIO-1347
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] [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug DEBIO-1347
 Drug Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
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.V555M (c.1663G>A) in gene FGFR3 cause the resistance of DEBIO-1347 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
Disease Class: Myeloproliferative neoplasm [ICD-11: 2A22.0] [4]
Sensitive Disease Myeloproliferative neoplasm [ICD-11: 2A22.0]
 Disease Info 
Sensitive Drug DEBIO-1347
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
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
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug DEBIO-1347
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
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.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of DEBIO-1347 by aberration of the drug's therapeutic target
LY-2874455
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: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug LY-2874455
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
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.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug LY-2874455
 Drug Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
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.V555M (c.1663G>A) in gene FGFR3 cause the sensitivity of LY-2874455 by aberration of the drug's therapeutic target
Preclinical Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
FIIN-2
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] [2]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Resistant Drug FIIN-2
 Drug Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 8UDV
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.03
TM score: 0.90455
Amino acid change:
V555M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
-
S
-
H
-
450
|
M
-
L
-
A
-
G
-
V
M
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
C
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
M
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
S
P
G
G
-
L
-
D
-
Y
-
S
-
F
-
580
|
D
-
T
-
C
-
K
-
P
-
P
-
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
K
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
H
D
H
E
H
760
|
-
H
-
H
-
H
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.V555M (c.1663G>A) in gene FGFR3 cause the resistance of FIIN-2 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
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug FIIN-2
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
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.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of FIIN-2 by aberration of the drug's therapeutic target
SU5402
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: Myeloproliferative neoplasm [ICD-11: 2A22.0] [5]
Sensitive Disease Myeloproliferative neoplasm [ICD-11: 2A22.0]
 Disease Info 
Sensitive Drug SU5402
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
E
E
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Blood vessel N.A.
Experiment for
Molecule Alteration		 Mass spectrum assay
Experiment for
Drug Resistance		 CellTiter 96 aqueous one solution cell proliferation assay
Mechanism Description The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of SU5402 by aberration of the drug's therapeutic target
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
PD98059
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: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [6]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug PD98059
 Drug Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.53  Å
PDB: 6LVM
Mutant Type Structure Method: X-ray diffraction Resolution: 2.34  Å
PDB: 4K33
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.96738
Amino acid change:
K650E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
440
|
-
H
-
H
-
H
-
H
-
H
-
S
-
Q
G
D
S
P
H
P
450
|
M
T
L
L
A
A
G
N
V
V
S
S
E
E
Y
L
E
E
L
L
460
|
P
P
E
A
D
D
P
P
K
K
W
W
E
E
F
L
P
S
R
R
470
|
D
A
K
R
L
L
T
T
L
L
G
G
K
K
P
P
L
L
G
G
480
|
E
E
G
G
C
A
F
F
G
G
Q
Q
V
V
V
V
M
M
A
A
490
|
E
E
A
A
I
I
G
G
I
I
D
D
K
K
D
D
R
R
A
A
500
|
A
A
K
K
P
P
V
V
T
T
V
V
A
A
V
V
K
K
M
M
510
|
L
L
K
K
D
D
D
D
A
A
T
T
D
D
K
K
D
D
L
L
520
|
S
S
D
D
L
L
V
V
S
S
E
E
M
M
E
E
M
M
M
M
530
|
K
K
M
M
I
I
G
G
K
K
H
H
K
K
N
N
I
I
I
I
540
|
N
N
L
L
L
L
G
G
A
A
C
C
T
T
Q
Q
G
G
G
G
550
|
P
P
L
L
Y
Y
V
V
L
L
V
V
E
E
Y
Y
A
A
A
A
560
|
K
K
G
G
N
N
L
L
R
R
E
E
F
F
L
L
R
R
A
A
570
|
R
R
R
R
P
P
P
P
G
G
L
L
D
D
Y
Y
S
S
F
F
580
|
D
D
T
T
C
S
K
K
P
P
P
P
E
E
E
E
Q
Q
L
L
590
|
T
T
F
F
K
K
D
D
L
L
V
V
S
S
C
C
A
A
Y
Y
600
|
Q
Q
V
V
A
A
R
R
G
G
M
M
E
E
Y
Y
L
L
A
A
610
|
S
S
Q
Q
K
K
C
C
I
I
H
H
R
R
D
D
L
L
A
A
620
|
A
A
R
R
N
N
V
V
L
L
V
V
T
T
E
E
D
D
N
N
630
|
V
V
M
M
K
K
I
I
A
A
D
D
F
F
G
G
L
L
A
A
640
|
R
R
D
D
V
V
H
H
N
N
L
L
D
D
Y
Y
Y
Y
K
K
650
|
K
E
T
T
T
T
N
N
G
G
R
R
L
L
P
P
V
V
K
K
660
|
W
W
M
M
A
A
P
P
E
E
A
A
L
L
F
F
D
D
R
R
670
|
V
V
Y
Y
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
680
|
F
F
G
G
V
V
L
L
L
L
W
W
E
E
I
I
F
F
T
T
690
|
L
L
G
G
G
G
S
S
P
P
Y
Y
P
P
G
G
I
I
P
P
700
|
V
V
E
E
E
E
L
L
F
F
K
K
L
L
L
L
K
K
E
E
710
|
G
G
H
H
R
R
M
M
D
D
K
K
P
P
A
A
N
N
C
C
720
|
T
T
H
H
D
D
L
L
Y
Y
M
M
I
I
M
M
R
R
E
E
730
|
C
C
W
W
H
H
A
A
A
A
P
P
S
S
Q
Q
R
R
P
P
740
|
T
T
F
F
K
K
Q
Q
L
L
V
V
E
E
D
D
L
L
D
D
750
|
R
R
V
V
L
L
T
T
V
V
T
T
S
S
T
T
D
D
E
E
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
COS-1 cells Kidney Chlorocebus aethiops (Green monkey) CVCL_0223
Experiment for
Molecule Alteration		 Immunoprecipitation and immunoblot analysis
Mechanism Description The missense mutation p.K650E (c.1948A>G) in gene FGFR3 cause the sensitivity of PD98059 by unusual activation of pro-survival pathway
References
Ref 1 Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical useOncotarget. 2016 Apr 26;7(17):24252-68. doi: 10.18632/oncotarget.8132.
Ref 2 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 3 Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with FGFR3 AlterationsCancer Discov. 2018 Jul;8(7):812-821. doi: 10.1158/2159-8290.CD-18-0229. Epub 2018 May 30.
Ref 4 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 5 Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric propertiesCancer Cell. 2013 Apr 15;23(4):477-88. doi: 10.1016/j.ccr.2013.02.019.
Ref 6 The phosphotyrosine phosphatase SHP2 is a critical mediator of transformation induced by the oncogenic fibroblast growth factor receptor 3Oncogene. 2003 Oct 9;22(44):6909-18. doi: 10.1038/sj.onc.1206798.

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