Drug Information

Drug (ID: DG01535) and It's Reported Resistant Information
Name
RO-5126766 free base
Synonyms
946128-88-7; RO5126766; RO-5126766; CH5126766; Ro 5126766; RO-5126766 free base; RO5126766(CH5126766); CHEBI:78825; CH-5126766; Ro 5126766 - Bio-X; RG-7304; CKI-27; 3-[[2-[(methylaminosulfonyl)amino]-3-fluoropyridin-4-yl]methyl]-4-methyl-7-[(pyrimidin-2-yl)oxy]-2H-1-benzopyran-2-one; CHEMBL3264002; UNII-D0D4252V97; RO5126766 (CH5126766); D0D4252V97; VS-6766; N-(3-Fluoro-4-{[4-Methyl-2-Oxo-7-(Pyrimidin-2-Yloxy)-2h-Chromen-3-Yl]methyl}pyridin-2-Yl)-N'-Methylsulfuric Diamide; avutometinib; 3wig; CHU; SCHEMBL960093; GTPL11867; BCP21067; EX-A2151; BDBM50010462; NSC758248; NSC800871; s7170; ZINC68247388; AKOS030527032; CCG-269457; compound 1 [PMID: 24900832]; CS-5254; DB15254; NSC-758248; NSC-800871; SB16628; DA-40233; HY-18652; B5820; CH 5126766; FT-0737411; R-7304; A916428; RO5126766; CH5126766; Q27147976; RO 5126766; RO5126766; CH5126766; CH5126766; CH 5126766; 3-[(2-((N-methylsulfamoyl)amino)-3-fluoropyridin-4-yl)methyl]-4-methyl-7-(pyrimidin-2-yloxy)-chromen-2-one; 3-[[3-fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]-4-methyl-7-pyrimidin-2-yloxychromen-2-one; Sulfamide, N-(3-fluoro-4-((4-methyl-2-oxo-7-(2-pyrimidinyloxy)-2H-1-benzopyran-3-yl)methyl)-2-pyridinyl)-N'-methyl-
    Click to Show/Hide
Indication
In total 1 Indication(s)
Bacterial infection [ICD-11: 1A00-1C4Z]
Phase 2
[1]
Structure
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
7
IsoSMILES
CC1=C(C(=O)OC2=C1C=CC(=C2)OC3=NC=CC=N3)CC4=C(C(=NC=C4)NS(=O)(=O)NC)F
InChI
InChI=1S/C21H18FN5O5S/c1-12-15-5-4-14(31-21-25-7-3-8-26-21)11-17(15)32-20(28)16(12)10-13-6-9-24-19(18(13)22)27-33(29,30)23-2/h3-9,11,23H,10H2,1-2H3,(H,24,27)
InChIKey
LMMJFBMMJUMSJS-UHFFFAOYSA-N
PubChem CID
16719221
ChEBI ID
CHEBI:78825
TTD Drug ID
D05GQD
DrugBank ID
DB15254
Type(s) of Resistant Mechanism of This Drug
  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
Melanoma [ICD-11: 2C30]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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570
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580
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600
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720
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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
Endometrial cancer [ICD-11: 2C76]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
 Disease Info 
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
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
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M
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A
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E
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E
E
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330
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R
N
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V
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T
T
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F
E
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A
A
G
G
E
E
340
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Y
T
T
C
C
L
L
A
A
G
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S
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I
G
G
350
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I
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L
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-
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
Thyroid cancer [ICD-11: 2D10]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
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A
570
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I
I
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R
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580
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E
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D
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F
F
G
G
L
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T
T
600
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S
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W
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F
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G
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M
M
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A
P
P
E
E
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I
I
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D
630
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K
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Y
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D
V
V
640
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Y
Y
A
A
F
F
G
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V
L
L
Y
Y
E
E
L
L
650
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M
M
T
T
G
G
Q
Q
L
L
P
P
Y
Y
S
S
N
N
I
I
660
|
N
N
N
N
R
R
D
D
Q
Q
I
I
I
I
F
F
M
M
V
V
670
|
G
G
R
R
G
G
Y
Y
L
L
S
S
P
P
D
D
L
L
S
S
680
|
K
K
V
V
R
R
S
S
N
N
C
C
P
P
K
K
A
A
M
M
690
|
K
K
R
R
L
L
M
M
A
A
E
E
C
C
L
L
K
K
K
K
700
|
K
K
R
R
D
D
E
E
R
R
P
P
L
L
F
F
P
P
Q
Q
710
|
I
I
L
L
A
A
S
S
I
I
E
E
L
L
L
L
A
A
R
R
720
|
S
S
L
L
P
P
K
K
I
I
H
H
R
R
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ERK signaling pathway Inhibition hsa04210
References
Ref 1 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 2 Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodineJ Clin Invest. 2016 Nov 1;126(11):4119-4124. doi: 10.1172/JCI89067. Epub 2016 Sep 26.

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