Drug Information

Drug (ID: DG01584) and It's Reported Resistant Information
Name
LY-2874455
Synonyms
LY2874455; 1254473-64-7; LY-2874455; UNII-E9M363811V; LY 2874455; CHEMBL3828009; E9M363811V; (R,E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol; C21H19Cl2N5O2; (R,E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol.; 2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol; (R,E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)-ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol; LY2874455 monohydrate; SCHEMBL298445; SCHEMBL298446; GTPL8104; QCR-90; DTXSID20154776; BCP04756; EX-A1340; 2529AH; BDBM50189781; NSC771750; NSC783670; s7057; ZINC73069242; AKOS027251051; BCP9000878; CCG-269169; CS-0907; DB13022; LM 1476; NSC-771750; NSC-783670; (R,E)-2-(4-(2-(5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethan-1-ol; AC-33003; AS-74798; HY-13304; BCP0726000015; C72002; LY2874455/LY-2874455; J-690104; Q27082753; (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3-yl)vinyl)-1H-pyrazol-1-yl)ethanol; 2-{4-[(1E)-2-{5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl}ethenyl]-1H-pyrazol-1-yl}ethan-1-ol
    Click to Show/Hide
Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Target Fibroblast growth factor receptor 2 (FGFR2) FGFR2_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
7
IsoSMILES
C[C@H](C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3/C=C/C4=CN(N=C4)CCO
InChI
InChI=1S/C21H19Cl2N5O2/c1-13(21-17(22)10-24-11-18(21)23)30-15-3-5-20-16(8-15)19(26-27-20)4-2-14-9-25-28(12-14)6-7-29/h2-5,8-13,29H,6-7H2,1H3,(H,26,27)/b4-2+/t13-/m1/s1
InChIKey
GKJCVYLDJWTWQU-CXLRFSCWSA-N
PubChem CID
46944259
DrugBank ID
DB13022
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
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
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.N540K (c.1620C>G)
 Molecule Info 
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.N540K (c.1620C>G) in gene FGFR3 cause the resistance of LY-2874455 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
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.K650E (c.1948A>G)
 Molecule Info 
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
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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
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V555M (c.1663G>A)
 Molecule Info 
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
Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L608V (c.1822T>G)
 Molecule Info 
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.L608V (c.1822T>G) in gene FGFR3 cause the sensitivity of LY-2874455 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.

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