Drug Information

Drug (ID: DG01513) and It's Reported Resistant Information
Name
Regorafenib
Synonyms
Regorafenib; 755037-03-7; BAY 73-4506; Stivarga; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; Regorafenibum; Regorafenib (BAY 73-4506); BAY73-4506; UNII-24T2A1DOYB; 4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; BAY-73-4506; Regorafenib-13C-d3; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; 24T2A1DOYB; CHEMBL1946170; CHEBI:68647; Stivarga (TN); 4-(4-(((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)amino)-3-fluorophenoxy)-n-methylpyridine-2-carboxamide; Regorafenib [USAN:INN]; Fluoro-Sorafenib; 4-(4-(((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl}amino)-3-fluorophenoxy)-N-methylpyridine-2-carboxamide; Regorafenib (USAN/INN); RegorafenibBAY73-4506; MLS006010303; C21H15ClF4N4O3; Regorafenib crystalline form I; SCHEMBL432230; Regorafenib,BAY 73-4506; GTPL5891; QCR-85; Bay-734506; DTXSID60226441; EX-A058; Regorafenib - BAY 73-4506; SYN1169; BCPP000352; HMS3654K16; HMS3672E15; AOB87754; BCP02105; BKD17855; ZINC6745272; BDBM50363397; MFCD16038047; NSC763932; NSC800865; s1178; AKOS015951107; AM81251; BAY 734506; BCP9000384; CCG-269571; CS-0170; DB08896; NSC-763932; NSC-800865; SB16819; NCGC00263138-01; NCGC00263138-13; NCGC00263138-19; 2-Pyridinecarboxamide,4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]-3-fluorophenoxy]-N-methyl-; AC-25075; AC-31116; AS-16304; HY-10331; SMR004701370; FT-0674338; R0142; SW218097-2; cas:835621-07-3;Regorafenib hydrochloride; Regorafenib (BAY73-4506,Fluoro-Sorafenib); A25020; D10138; AB01565826_02; SR-01000941571; Q3891664; SR-01000941571-1; BRD-K16730910-001-02-4; 2-Pyridinecarboxamide, 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]-3-fluorophenoxy]-N-methyl-; 4-[4-({[4-Chloro-3-(trifluoromethy)phenyl]carbamoyl}amino)-3-fluorophenoxy]-1-methylpyridine-2-carboxamide; 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide; 835621-08-4; Regorafenib;1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-fluoro-4-(2-(methylcarbamoyl)pyridin-4-yloxy)phenyl)urea
    Click to Show/Hide
Indication
In total 1 Indication(s)
Metastatic colorectal cancer [ICD-11: 2D85]
Phase 2
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (5 diseases)
Colorectal cancer [ICD-11: 2B91]
[2]
Gastrointestinal cancer [ICD-11: 2B5B]
[3]
Liver cancer [ICD-11: 2C12]
[4]
Mastocytosis [ICD-11: 2A21]
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[5]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (3 diseases)
Colorectal cancer [ICD-11: 2B91]
[6]
Liver cancer [ICD-11: 2C12]
[4]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[7]
Target Proto-oncogene c-Ret (RET) RET_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
5
IsoSMILES
CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F
InChI
InChI=1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
InChIKey
FNHKPVJBJVTLMP-UHFFFAOYSA-N
PubChem CID
11167602
ChEBI ID
CHEBI:68647
VARIDT ID
DR1401
INTEDE ID
DR00136
DrugBank ID
DB08896
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: MAPK/ERK kinase 1 (MEK1) [7]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.C121S (c.361T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 7B7R
Mutant Type Structure Method: X-ray diffraction Resolution: 2.01  Å
PDB: 7F2X
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.36
TM score: 0.87257
Amino acid change:
C121S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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20
|
M
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A
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H
-
H
-
H
-
H
-
H
-
H
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A
-
A
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30
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A
-
E
-
N
-
L
-
Y
-
F
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Q
-
L
-
E
-
E
-
40
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L
-
E
-
L
M
D
T
E
L
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Q
Q
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K
K
R
R
50
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L
L
E
E
A
A
F
F
L
L
T
T
Q
Q
K
K
Q
Q
K
K
60
|
V
V
G
G
E
E
L
L
K
K
D
D
D
D
D
D
F
F
E
E
70
|
K
K
I
I
S
S
E
E
L
L
G
G
A
A
G
G
N
N
G
G
80
|
G
G
V
V
V
V
F
F
K
K
V
V
S
S
H
H
K
K
P
P
90
|
S
S
G
G
L
L
V
V
M
M
A
A
R
R
K
K
L
L
I
I
100
|
H
H
L
L
E
E
I
I
K
K
P
P
A
A
I
I
R
R
N
N
110
|
Q
Q
I
I
I
I
R
R
E
E
L
L
Q
Q
V
V
L
L
H
H
120
|
E
E
C
S
N
N
S
S
P
P
Y
Y
I
I
V
V
G
G
F
F
130
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Y
Y
G
G
A
A
F
F
Y
Y
S
S
D
D
G
G
E
E
I
I
140
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S
S
I
I
C
C
M
M
E
E
H
H
M
M
D
D
G
G
G
G
150
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S
S
L
L
D
D
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Q
V
V
L
L
K
K
K
K
A
A
G
G
160
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R
R
I
I
P
P
E
E
Q
Q
I
I
L
L
G
G
K
K
V
V
170
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S
S
I
I
A
A
V
V
I
I
K
K
G
G
L
L
T
T
Y
Y
180
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L
L
R
R
E
E
K
K
H
H
K
K
I
I
M
M
H
H
R
R
190
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D
D
V
V
K
K
P
P
S
S
N
N
I
I
L
L
V
V
N
N
200
|
S
S
R
R
G
G
E
E
I
I
K
K
L
L
C
C
D
D
F
F
210
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G
G
V
V
S
S
G
G
Q
Q
L
L
I
I
D
D
S
S
M
M
220
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A
A
N
N
S
S
F
F
V
V
G
G
T
T
R
R
S
S
Y
Y
230
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M
M
S
S
P
P
E
E
R
R
L
L
Q
Q
G
G
T
T
H
H
240
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Y
Y
S
S
V
V
Q
Q
S
S
D
D
I
I
W
W
S
S
M
M
250
|
G
G
L
L
S
S
L
L
V
V
E
E
M
M
A
A
V
V
G
G
260
|
R
R
Y
Y
P
P
I
I
-
G
-
S
-
G
-
S
-
G
-
S
270
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-
M
-
A
-
I
-
F
-
E
-
L
-
L
-
D
-
Y
-
I
280
|
-
V
-
N
-
E
-
P
-
P
-
P
-
K
-
L
-
P
-
S
290
|
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G
-
V
-
F
-
S
-
L
-
E
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F
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D
-
F
300
|
-
V
-
N
G
K
S
C
G
L
S
I
G
K
S
N
M
P
A
A
310
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I
E
F
R
E
A
L
D
L
L
D
K
Y
Q
I
L
V
M
N
V
320
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E
H
P
A
P
F
P
I
K
K
L
R
P
S
S
D
G
A
V
E
330
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F
E
S
V
L
D
E
F
F
A
Q
G
D
W
F
L
V
C
N
S
340
|
K
T
C
I
L
G
I
L
K
N
N
Q
P
P
A
S
E
T
R
P
350
|
A
T
D
H
L
A
K
A
Q
G
L
E
M
G
V
H
H
H
A
H
360
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F
H
I
H
K
H
R
-
S
-
D
-
A
-
E
-
E
-
V
-
370
|
D
-
F
-
A
-
G
-
W
-
L
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C
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S
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T
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I
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380
|
G
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L
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N
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Q
-
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 SDS-PAGE assay
Mechanism Description The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of Regorafenib by unusual activation of pro-survival pathway
Gastrointestinal cancer [ICD-11: 2B5B]
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: Mast/stem cell growth factor receptor Kit (KIT) [8]
Sensitive Disease Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T670I (c.2009C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.25  Å
PDB: 6HH1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 8PQG
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.88
TM score: 0.9084
Amino acid change:
T670I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
G
-
S
550
|
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M
-
P
-
M
-
Y
-
E
-
V
-
Q
-
W
-
K
-
V
560
|
-
V
-
E
-
E
-
S
-
N
G
G
N
N
N
N
Y
Y
V
S
570
|
Y
Y
I
I
D
D
P
P
T
T
Q
Q
L
L
P
P
Y
Y
D
D
580
|
H
H
K
K
W
W
E
E
F
F
P
P
R
R
N
N
R
R
L
L
590
|
S
S
F
F
G
G
K
K
T
T
L
L
G
G
A
A
G
G
A
A
600
|
F
F
G
G
K
K
V
V
V
V
E
E
A
A
T
T
A
A
Y
Q
610
|
G
G
L
L
I
I
K
K
S
S
D
D
A
A
A
A
M
M
T
T
620
|
V
V
A
A
V
V
K
K
M
M
L
L
K
K
P
P
S
S
A
A
630
|
H
H
L
S
T
T
E
E
R
R
E
E
A
A
L
L
M
M
S
S
640
|
E
E
L
L
K
K
V
V
L
L
S
S
Y
Y
L
L
G
G
N
N
650
|
H
H
M
E
N
N
I
I
V
V
N
N
L
L
L
L
G
G
A
A
660
|
C
C
T
T
I
H
G
G
G
G
P
P
T
T
L
L
V
V
I
I
670
|
T
I
E
E
Y
Y
C
C
C
C
Y
Y
G
G
D
D
L
L
L
L
680
|
N
N
F
F
L
L
R
R
R
R
K
K
R
R
D
D
S
E
F
F
690
|
I
V
C
P
S
Y
K
K
T
-
-
-
-
-
-
-
-
-
-
-
700
|
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
710
|
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
720
|
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
730
|
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-
-
-
-
-
-
-
-
-
-
-
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-
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-
-
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-
-
740
|
-
-
-
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-
-
-
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-
-
-
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-
-
-
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-
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750
|
-
-
-
-
-
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S
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P
V
A
A
I
P
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E
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D
-
L
760
|
-
Y
E
K
L
D
A
F
L
L
D
T
L
L
E
E
D
H
L
L
770
|
L
L
S
S
F
F
S
S
Y
Y
Q
Q
V
V
A
A
K
K
G
G
780
|
M
M
A
A
F
F
L
L
A
A
S
S
K
K
N
N
C
C
I
I
790
|
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
I
I
L
L
800
|
L
L
T
T
H
H
G
G
R
N
I
I
T
T
K
K
I
I
C
C
810
|
D
D
F
F
G
G
L
L
A
A
R
R
D
D
I
I
K
K
N
N
820
|
D
D
S
S
N
N
Y
Y
V
V
V
D
K
K
G
G
N
N
A
A
830
|
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
E
E
840
|
S
S
I
I
F
F
N
N
C
S
V
V
Y
Y
T
T
F
F
E
E
850
|
S
S
D
D
V
V
W
W
S
S
Y
Y
G
G
I
I
F
F
L
L
860
|
W
W
E
E
L
L
F
F
S
S
L
L
G
G
S
S
S
S
P
P
870
|
Y
Y
P
P
G
G
M
M
P
P
V
V
D
D
S
S
K
K
F
F
880
|
Y
Y
K
K
M
M
I
I
K
K
E
E
G
G
F
F
R
R
M
M
890
|
L
S
S
S
P
P
E
E
H
Y
A
A
P
P
A
A
E
E
M
M
900
|
Y
Y
D
D
I
I
M
M
K
K
T
T
C
C
W
W
D
D
A
A
910
|
D
D
P
P
L
D
K
K
R
R
P
P
T
T
F
F
K
K
Q
Q
920
|
I
I
V
V
Q
Q
L
D
I
I
E
E
K
K
Q
Q
I
I
S
S
930
|
-
E
-
S
-
T
-
N
-
H
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Colorectal cancer [ICD-11: 2B91]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase KRas (KRAS) [6]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G12V (c.35G>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.98  Å
PDB: 7SCW
Mutant Type Structure Method: X-ray diffraction Resolution: 1.96  Å
PDB: 7SCX
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.47
TM score: 0.99104
Amino acid change:
G12V
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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G
-
0
|
S
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
V
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
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D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
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Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
S
S
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
170
|
M
M
S
S
K
K
D
D
G
G
K
K
K
K
K
K
K
K
K
K
180
|
K
K
S
S
K
K
T
T
K
K
C
C
V
V
I
I
M
M
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KRAS cells N.A. N.A. N.A.
G12C cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 KRAS testing/KRAS quantification assay
Experiment for
Drug Resistance		 MTT assay
Key Molecule: GTPase KRas (KRAS) [6]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G12R (c.34G>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 6VJJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.50  Å
PDB: 6CU6
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.17
TM score: 0.95613
Amino acid change:
G12R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
G
G
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
R
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KRAS cells N.A. N.A. N.A.
G12C cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 KRAS testing/KRAS quantification assay
Experiment for
Drug Resistance		 MTT assay
Key Molecule: GTPase KRas (KRAS) [6]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G12A (c.35G>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 6VJJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.45  Å
PDB: 8TBJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.06
TM score: 0.96454
Amino acid change:
G12A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
G
S
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
A
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KRAS cells N.A. N.A. N.A.
G12C cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 KRAS testing/KRAS quantification assay
Experiment for
Drug Resistance		 MTT assay
Key Molecule: GTPase KRas (KRAS) [6]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G12C (c.34G>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 6VJJ
Mutant Type Structure Method: X-ray diffraction Resolution: 1.60  Å
PDB: 8JGD
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.55
TM score: 0.93157
Amino acid change:
G12C
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
G
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
C
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
R
V
V
D
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
Q
H
Y
K
R
E
L
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KRAS cells N.A. N.A. N.A.
G12C cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 KRAS testing/KRAS quantification assay
Experiment for
Drug Resistance		 MTT assay
Key Molecule: GTPase KRas (KRAS) [6]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G12S (c.34G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.24  Å
PDB: 4OBE
Mutant Type Structure Method: X-ray diffraction Resolution: 1.71  Å
PDB: 7TLK
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.85
TM score: 0.93473
Amino acid change:
G12S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
S
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
G
V
V
D
D
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
K
H
H
K
K
E
E
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KRAS cells N.A. N.A. N.A.
G12C cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 KRAS testing/KRAS quantification assay
Experiment for
Drug Resistance		 MTT assay
Key Molecule: GTPase KRas (KRAS) [6]
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G12D (c.35G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 6VJJ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 8JHL
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.55
TM score: 0.9318
Amino acid change:
G12D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
0
|
G
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
|
G
G
A
A
G
D
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
|
T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
|
D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
|
Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
|
T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
|
G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
|
Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
|
C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
|
F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
|
I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
|
P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
|
L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
|
A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
|
P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
|
Q
Q
G
R
V
V
D
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
|
V
V
R
R
E
E
I
I
R
R
K
Q
H
Y
K
R
E
L
K
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KRAS cells N.A. N.A. N.A.
G12C cells N.A. N.A. N.A.
Experiment for
Molecule Alteration		 KRAS testing/KRAS quantification assay
Experiment for
Drug Resistance		 MTT assay
References
Ref 1 Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA VariantsCancer Cell. 2019 May 13;35(5):738-751.e9. doi: 10.1016/j.ccell.2019.04.006.
Ref 2 Exome Sequencing of Plasma DNA Portrays the Mutation Landscape of Colorectal Cancer and Discovers Mutated VEGFR2 Receptors as Modulators of Antiangiogenic TherapiesClin Cancer Res. 2018 Aug 1;24(15):3550-3559. doi: 10.1158/1078-0432.CCR-18-0103. Epub 2018 Mar 27.
Ref 3 Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trialJ Clin Oncol. 2012 Jul 1;30(19):2401-7. doi: 10.1200/JCO.2011.39.9394. Epub 2012 May 21.
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