Drug Information

Drug (ID: DG01574) and It's Reported Resistant Information
Name
TAK-632
Synonyms
TAK-632; 1228591-30-7; TAK632; N-(7-cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide; N-{7-Cyano-6-[4-Fluoro-3-({[3-(Trifluoromethyl)phenyl]acetyl}amino)phenoxy]-1,3-Benzothiazol-2-Yl}cyclopropanecarboxamide; N-[7-CYANO-6-(4-FLUORO-3-{2-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDO}PHENOXY)-1,3-BENZOTHIAZOL-2-YL]CYCLOPROPANECARBOXAMIDE; N-[7-cyano-6-[4-fluoro-3-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1,3-benzothiazol-2-yl]cyclopropanecarboxamide; C27H18F4N4O3S; 4ksp; 1SU; N-[7-Cyano-6-[4-fluoro-3-[[[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1,3-benzothiazol-2-yl]cyclopropanecarboxamide; SCHEMBL823682; CHEMBL3125890; BDBM99471; GTPL10387; EX-A242; SYN1203; TAK 632; CHEBI:167673; HMS3653M08; HMS3673M07; AOB87729; BCP08426; TAK 632; TAK 632; 2742AH; MFCD26960965; NSC778809; s7291; ZINC68208189; AKOS025405225; CCG-270021; CS-1697; NSC-778809; compound 8B [PMID: 23906342]; NCGC00371156-09; AS-16332; DA-47029; HY-15767; QC-10896; FT-0700129; SW219895-1; US8497274, 32; A890929; J-690078; Q27452417; Benzeneacetamide, N-[5-[[7-cyano-2-[(cyclopropylcarbonyl)amino]-6-benzothiazolyl]oxy]-2-fluorophenyl]-3-(trifluoromethyl)-; N-[5-[[7-cyano-2-[(cyclopropylcarbonyl)amino]-6-benzothiazolyl]oxy]-2-fluorophenyl]-3-(trifluoromethyl)-benzeneacetamide
    Click to Show/Hide
Structure
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
7
IsoSMILES
C1CC1C(=O)NC2=NC3=C(S2)C(=C(C=C3)OC4=CC(=C(C=C4)F)NC(=O)CC5=CC(=CC=C5)C(F)(F)F)C#N
InChI
InChI=1S/C27H18F4N4O3S/c28-19-7-6-17(12-21(19)33-23(36)11-14-2-1-3-16(10-14)27(29,30)31)38-22-9-8-20-24(18(22)13-32)39-26(34-20)35-25(37)15-4-5-15/h1-3,6-10,12,15H,4-5,11H2,(H,33,36)(H,34,35,37)
InChIKey
OJFKUJDRGJSAQB-UHFFFAOYSA-N
PubChem CID
46209401
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
Colorectal cancer [ICD-11: 2B91]
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: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 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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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
Hth104 cells Thyroid gland Homo sapiens (Human) CVCL_A427
In Vivo Model Mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of TAK-632 by aberration of the drug's therapeutic target
Lung cancer [ICD-11: 2C25]
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: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G466V (c.1397G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
Hth104 cells Thyroid gland Homo sapiens (Human) CVCL_A427
In Vivo Model Mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.G466V (c.1397G>T) in gene BRAF cause the sensitivity of TAK-632 by aberration of the drug's therapeutic target
Melanoma [ICD-11: 2C30]
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: 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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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
Hth104 cells Thyroid gland Homo sapiens (Human) CVCL_A427
In Vivo Model Mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of TAK-632 by aberration of the drug's therapeutic target
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G466E (c.1397G>A)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
Hth104 cells Thyroid gland Homo sapiens (Human) CVCL_A427
In Vivo Model Mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.G466E (c.1397G>A) in gene BRAF cause the sensitivity of TAK-632 by aberration of the drug's therapeutic target
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600R (c.1798_1799delGTinsAG)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
Hth104 cells Thyroid gland Homo sapiens (Human) CVCL_A427
In Vivo Model Mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.V600R (c.1798_1799delGTinsAG) in gene BRAF cause the sensitivity of TAK-632 by aberration of the drug's therapeutic target
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Molecule Alteration Missense mutation
p.V600D (c.1799_1800delTGinsAC)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
Hth104 cells Thyroid gland Homo sapiens (Human) CVCL_A427
In Vivo Model Mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.V600D (c.1799_1800delTGinsAC) in gene BRAF cause the sensitivity of TAK-632 by aberration of the drug's therapeutic target
Thyroid cancer [ICD-11: 2D10]
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: Serine/threonine-protein kinase B-raf (BRAF) [1]
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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K
S
S
I
I
I
I
H
H
R
R
D
D
L
L
K
K
S
S
580
|
N
N
N
N
I
I
F
F
L
L
H
H
E
E
D
D
L
L
T
T
590
|
V
V
K
K
I
I
G
G
D
D
F
F
G
G
L
L
A
A
T
T
600
|
V
E
K
K
S
S
R
R
W
W
S
S
G
G
S
S
H
H
Q
Q
610
|
F
F
E
E
Q
Q
L
L
S
S
G
G
S
S
I
I
L
L
W
W
620
|
M
M
A
A
P
P
E
E
V
V
I
I
R
R
M
M
Q
Q
D
D
630
|
K
K
N
N
P
P
Y
Y
S
S
F
F
Q
Q
S
S
D
D
V
V
640
|
Y
Y
A
A
F
F
G
G
I
I
V
V
L
L
Y
Y
E
E
L
L
650
|
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 Identified from the Human Clinical Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
8505C cells Thyroid Homo sapiens (Human) CVCL_1054
Hth104 cells Thyroid gland Homo sapiens (Human) CVCL_A427
In Vivo Model Mouse xenograft model Mus musculus
Mechanism Description The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of TAK-632 by aberration of the drug's therapeutic target
References
Ref 1 An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF SignalingCancer Cell. 2016 Sep 12;30(3):485-498. doi: 10.1016/j.ccell.2016.06.024. Epub 2016 Aug 11.

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