Drug Information

Drug (ID: DG01543) and It's Reported Resistant Information
Name
Apalutamide
Synonyms
Apalutamide; ARN-509; 956104-40-8; Erleada; ARN 509; JNJ-56021927; ARN509; Apalutamide (ARN-509); UNII-4T36H88UA7; 4-(7-(6-CYANO-5-(TRIFLUOROMETHYL)PYRIDIN-3-YL)-8-OXO-6-THIOXO-5,7-DIAZASPIRO[3.4]OCTAN-5-YL)-2-FLUORO-N-METHYLBENZAMIDE; 4T36H88UA7; 956104-40-8 (free base); 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide; 4-{7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl}-2-fluoro-N-methylbenzamide; Apalutamide [INN]; AR509; 4-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro(3.4)octan-5-yl)-2-fluoro-N-methylbenzamide; ApalutamideARN509; Erleada (TN); JNJ 56021927; Apalutamide (JAN/INN); MLS006011109; SCHEMBL909297; GTPL9043; C21H15F4N5O2S; CHEMBL3183409; DTXSID40241899; EX-A089; QCR-211; HMS3656N12; AMY24182; BCP05829; AR509/AR-509; BDBM50094975; MFCD22380626; NSC771649; NSC794776; s2840; ZINC43174901; AKOS025401932; CCG-264760; CS-0885; DB11901; NSC-771649; NSC-794776; PB27306; NCGC00346725-01; NCGC00346725-02; NCGC00346725-06; 4-(7-(6-cyano-5-(trifluoroMethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspirooctan-5-yl)-2-fluoro-N-MethylbenzaMide; AC-27403; AS-35181; HY-16060; SMR004702891; SW220300-1; Y0375; 24872560, Erleada, C21H15F4N5O2S; D11040; J-519596; Q21098975; Benzamide, 4-[7-[6-cyano-5-(trifluoromethyl)-3-pyridinyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methyl-
    Click to Show/Hide
Indication
In total 1 Indication(s)
Discovery agent [ICD-11: N.A.]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Prostate cancer [ICD-11: 2C82]
[1]
Target Extracellular signal-regulated kinase 2 (ERK2) MK01_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
3
IsoSMILES
CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F)F
InChI
InChI=1S/C21H15F4N5O2S/c1-27-17(31)13-4-3-11(8-15(13)22)30-19(33)29(18(32)20(30)5-2-6-20)12-7-14(21(23,24)25)16(9-26)28-10-12/h3-4,7-8,10H,2,5-6H2,1H3,(H,27,31)
InChIKey
HJBWBFZLDZWPHF-UHFFFAOYSA-N
PubChem CID
24872560
TTD Drug ID
D08XVZ
VARIDT ID
DR0121
DrugBank ID
DB11901
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  MRAP: Metabolic Reprogramming via Altered Pathways
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
Prostate cancer [ICD-11: 2C82]
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: Androgen receptor (AR) [1]
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Missense mutation
p.F877L (c.2629T>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.44  Å
PDB: 5V8Q
Mutant Type Structure Method: X-ray diffraction Resolution: 1.69  Å
PDB: 8FH1
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.7
TM score: 0.99191
Amino acid change:
F877L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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720
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730
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740
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750
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760
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R
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M
Y
L
F
Y
A
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A
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770
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F
E
N
Y
E
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Y
M
R
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M
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780
|
M
R
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M
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R
M
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790
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L
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E
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800
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T
I
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810
|
L
A
L
L
L
L
F
L
S
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I
S
I
I
P
I
V
P
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820
|
G
D
L
G
K
L
N
K
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N
K
Q
F
K
F
F
D
F
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830
|
L
E
R
L
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N
M
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N
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840
|
R
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A
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A
A
C
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K
R
N
K
P
N
850
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T
P
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R
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Y
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Y
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860
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870
|
A
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A
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880
|
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890
|
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900
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910
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Y
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920
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
PC3 cells Prostate Homo sapiens (Human) CVCL_0035
In Vivo Model SHO male mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Chromatin immunoprecipitation assay
Mechanism Description The missense mutation p.F877L (c.2629T>C) in gene AR cause the resistance of Apalutamide by aberration of the drug's therapeutic target
Key Molecule: Androgen receptor (AR) [1]
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Missense mutation
p.F877L (c.2629T>C)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.44  Å
PDB: 5V8Q
Mutant Type Structure Method: X-ray diffraction Resolution: 1.69  Å
PDB: 8FH1
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.7
TM score: 0.99191
Amino acid change:
F877L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
S
-
H
-
I
-
E
-
G
-
Y
-
E
670
|
-
C
P
Q
I
P
F
I
L
F
N
L
V
N
L
V
E
L
A
E
680
|
I
A
E
I
P
E
G
P
V
G
V
V
C
V
A
C
G
A
H
G
690
|
D
H
N
D
N
N
Q
N
P
Q
D
P
S
D
F
S
A
F
A
A
700
|
L
A
L
L
S
L
S
S
L
S
N
L
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N
L
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G
L
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G
710
|
R
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Q
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720
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730
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740
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750
|
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N
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760
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770
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780
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790
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800
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810
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L
L
L
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L
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F
I
S
I
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I
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P
D
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820
|
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D
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G
K
L
N
K
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N
K
Q
F
K
F
F
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830
|
L
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R
L
M
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N
M
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840
|
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D
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A
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K
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N
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850
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860
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K
T
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L
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P
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I
P
870
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A
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R
A
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R
L
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L
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F
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T
L
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880
|
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L
L
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K
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H
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H
V
M
S
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890
|
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F
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P
M
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M
M
A
M
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A
I
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I
900
|
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I
V
S
Q
V
V
Q
P
V
K
P
I
K
L
I
S
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910
|
K
G
V
K
K
V
P
K
I
P
Y
I
F
Y
H
F
T
H
Q
T
920
|
-
Q
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
PC3 cells Prostate Homo sapiens (Human) CVCL_0035
In Vivo Model SHO male mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Chromatin immunoprecipitation assay
Mechanism Description The missense mutation p.F877L (c.2629T>C) in gene AR cause the resistance of Apalutamide by aberration of the drug's therapeutic target
Key Molecule: Androgen receptor (AR) [1]
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Missense mutation
p.F877L (.
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
PC3 cells Prostate Homo sapiens (Human) CVCL_0035
In Vivo Model SHO male mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Chromatin immunoprecipitation assay
Mechanism Description The missense mutation p.F877L (. in gene AR cause the resistance of Apalutamide by aberration of the drug's therapeutic target
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]
Metabolic Type Mitochondrial metabolism
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration .
.
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model PNT1A cells Prostate Homo sapiens (Human) CVCL_2163
Experiment for
Drug Resistance		 Apoptosis rate assay
Mechanism Description Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [21]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.
Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]
Metabolic Type Mitochondrial metabolism
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration .
.
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
Experiment for
Drug Resistance		 Apoptosis rate assay
Mechanism Description Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [22]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.
Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]
Metabolic Type Mitochondrial metabolism
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration .
.
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model PC-3 cells Bone Homo sapiens (Human) CVCL_0035
Experiment for
Drug Resistance		 Apoptosis rate assay
Mechanism Description Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [23]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.
Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [2]
Metabolic Type Mitochondrial metabolism
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration .
.
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model C4-2 cells Prostate Homo sapiens (Human) CVCL_4782
Experiment for
Drug Resistance		 Apoptosis rate assay
Mechanism Description Recently, we have demonstrated that an inhibitor of the mitochondrial electron transport chain complex I IACS-010759 ('IACS') acts synergistically with ARN in reducing PCa cell growth [24]. In this study, we investigated the effects of ARN and IACS on the mitochondrial network architecture and dynamics in PCa cells. Additionally, we explored the effect of androgen in regulating the mitochondrial network dynamics and metabolic modulations of respiratory pathways.
References
Ref 1 A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509Cancer Discov. 2013 Sep;3(9):1020-9. doi: 10.1158/2159-8290.CD-13-0226. Epub 2013 Jun 18.
Ref 2 Mitochondrial Elongation and ROS-Mediated Apoptosis in Prostate Cancer Cells under Therapy with Apalutamide and Complex I Inhibitor. Int J Mol Sci. 2024 Jun 25;25(13):6939.

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