Drug Information

Drug (ID: DG00705) and It's Reported Resistant Information
Name
Bicalutamide
Synonyms
Bicalutamide; 90357-06-5; Casodex; Cosudex; Bicalutamide (CDX); Calutide; ICI 176334; ICI-176334; N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)sulfonyl-2-hydroxy-2-methylpropanamide; N-(4-cyano-3-(trifluoromethyl)phenyl)-3-((4-fluorophenyl)sulfonyl)-2-hydroxy-2-methylpropanamide; Bicalutamide (Casodex); CHEMBL409; ICI 176,334; MFCD00869971; N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide; NSC-759816; Raffolutil; Kalumid; SMR000466329; Casodex (TN); SR-01000759410; BRN 5364666; Bicalutamine; Bicalutamide (JAN/USP/INN); Propanamide,; CCRIS 8728; HSDB 7655; Bicalutamide [USAN:USP:INN:BAN]; (+-)-4'-Cyano-alpha,alpha,alpha-trifluoro-3-((p-fluorophenyl)sulfonyl)-2-methyl-m-lactotoluidide; KS-1161; Bicalutamide - Casodex; CPD000466329; SCHEMBL3611; (R)-(-)-Bicalutamide-d4; MLS000759437; MLS001424047; Propanamide, N-(4-cyano-3-(trifluoromethyl)phenyl)-3-((4-fluorophenyl)sulfonyl)-2-hydroxy-2-methyl-, (+-)-; S-(+)-Bicalutamide-[d4]; GTPL2863; DTXSID2022678; BDBM18525; CHEBI:91617; AOB5596; EX-A962; CHEBI:144093; BCPP000337; HMS2051B13; HMS2089N12; HMS2232H03; HMS3263M13; HMS3372K05; HMS3393B13; HMS3654K18; HMS3714P13; Pharmakon1600-01504827; ACT06291; AMY33430; BCP02110; Tox21_501026; NSC722665; NSC759816; s1190; AKOS015895073; AC-4232; BCP9000408; CCG-100951; CCG-220876; CCG-222330; CS-1296; DB01128; LP01026; NC00201; NSC 759816; NSC-722665; SB17301; SDCCGSBI-0633779.P001; N-(4-cyano-3-(trifluoromethyl)phenyl); NCGC00167977-01; NCGC00167977-02; NCGC00167977-03; NCGC00167977-09; NCGC00167977-20; NCGC00261711-01; HY-14249; ICI176,334-1; Propanamide, N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-; DB-041165; B3206; FT-0618286; FT-0631069; FT-0663100; SW197581-4; Bicalutamide (CDX), >=98% (HPLC), powder; C08160; D00961; J10442; AB00639963-06; AB00639963-08; AB00639963-09; AB00639963_10; 357B065; A803039; A843528; Q1988832; SR-01000759410-4; SR-01000759410-5; BRD-A29485665-001-03-7; Bicalutamide, British Pharmacopoeia (BP) Reference Standard; Bicalutamide, European Pharmacopoeia (EP) Reference Standard; Bicalutamide, United States Pharmacopeia (USP) Reference Standard; 4'-cyano-3-[(4- fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3'-trifluoromethylpropionanilide; 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3'-trifluoromethylpropionanilide; Bicalutamide for system suitability, European Pharmacopoeia (EP) Reference Standard; Bicalutamide, Pharmaceutical Secondary Standard; Certified Reference Material; N-(4-cyano-3-(trifluoromethyl)phenyl)-3-((4-fluorophenyl)sulfonyl)-2-hydroxy-2-methyl-N-phenylpropanamide; N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-fluorophenylsulfonyl)-2-hydroxy-2-methylpropanamide; N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenyl)sulfonyl-2-methyl-2-oxidanyl-propanamide; N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorobenzene)sulfonyl]-2-hydroxy-2-methylpropanamide; N-[4-Cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropionamide; N-[4-cyano-3-trifluoromethyl-phenyl]-3-[4-fluorophenyl-sulfonyl]-2-hydroxy-2-methyl-propionamide
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Indication
In total 1 Indication(s)
Prostate cancer [ICD-11: 2C82]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Prostate cancer [ICD-11: 2C82]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Prostate cancer [ICD-11: 2C82]
[2]
Target Androgen receptor (AR) ANDR_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C18H14F4N2O4S
IsoSMILES
CC(CS(=O)(=O)C1=CC=C(C=C1)F)(C(=O)NC2=CC(=C(C=C2)C#N)C(F)(F)F)O
InChI
1S/C18H14F4N2O4S/c1-17(26,10-29(27,28)14-6-3-12(19)4-7-14)16(25)24-13-5-2-11(9-23)15(8-13)18(20,21)22/h2-8,26H,10H2,1H3,(H,24,25)
InChIKey
LKJPYSCBVHEWIU-UHFFFAOYSA-N
PubChem CID
2375
ChEBI ID
CHEBI:91617
TTD Drug ID
D0V9BD
VARIDT ID
DR00795
INTEDE ID
DR0210
DrugBank ID
DB01128
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  MRAP: Metabolic Reprogramming via Altered Pathways
  RTDM: Regulation by the Disease Microenvironment
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]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Protocadherin beta-9 (PCDHB9) [1]
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Differential expression of the molecule in resistant disease
Classification of Disease Prostate cancer [ICD-11: 2C82]
The Specified Disease Prostate cancer
The Studied Tissue Prostate
The Expression Level of Disease Section Compare with the Healthy Individual Tissue
p-value: 1.81E-02
Fold-change: 7.01E-02
Z-score: 2.42E+00
Experimental Note Identified from the Human Clinical Data
In Vitro Model LN229 cells Brain Homo sapiens (Human) CVCL_0393
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Bicalutamide has been widely used as a first-line treatment for PCa. Although patients initially show a favorable response to bicalutamide treatment, PCa eventually acquires bicalutamide resistance. Several factors have been shown to be involved in bicalutamide resistance. However, the mechanism of bicalutamide resistance is not fully understood. In this study, the knockdown of protocadherin B9 reduced nuclear AR translocation and bicalutamide resistance in androgen-dependent LNCaP cells in the presence of DHT. The overexpression of protocadherin B9 had no effect on bicalutamide resistance in androgen-independent DU145 cells. These results further indicate that protocadherin B9 is involved in bicalutamide resistance through the modulation of AR signaling. Taken together, our findings suggest that protocadherin B9 targeted therapy could be more effective therapy than bicalutamide alone for patients with PCa.
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Androgen receptor (AR) [3]
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Missense mutation
p.W742L (c.2225G>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.07  Å
PDB: 5CJ6
Mutant Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 2AX8
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.43
TM score: 0.99443
Amino acid change:
W742L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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640
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S
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L
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E
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E
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G
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A
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650
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660
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L
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G
G
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Y
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E
670
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C
C
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F
F
L
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N
N
V
V
L
L
E
E
680
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A
A
I
I
E
E
P
P
G
G
V
V
V
V
C
C
A
A
G
G
690
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H
H
D
D
N
N
N
N
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Q
P
P
D
D
S
S
F
F
A
A
700
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A
A
L
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L
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L
L
N
N
E
E
L
L
G
G
710
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E
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R
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L
L
V
V
H
H
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V
V
K
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W
W
720
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A
A
K
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A
A
L
L
P
P
G
G
F
F
R
R
N
N
L
L
730
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H
V
V
D
D
D
D
Q
Q
M
M
A
A
V
V
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740
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Y
S
S
W
L
M
M
G
G
L
L
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A
A
750
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M
M
G
G
W
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R
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F
F
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N
N
V
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N
N
760
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S
S
R
R
M
M
L
L
Y
Y
F
F
A
A
P
P
D
D
L
L
770
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V
V
F
F
N
N
E
E
Y
Y
R
R
M
M
H
H
K
K
S
S
780
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R
R
M
M
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C
C
V
V
R
R
M
M
R
R
790
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L
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F
F
G
G
W
W
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800
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I
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E
F
F
L
L
C
C
M
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810
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A
A
L
L
L
L
L
L
F
F
S
S
I
I
I
I
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V
V
820
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D
D
G
G
L
L
K
K
N
N
Q
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K
K
F
F
F
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D
D
830
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E
E
L
L
R
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M
M
N
N
Y
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E
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L
840
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D
D
R
R
I
I
I
I
A
A
C
C
K
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R
R
K
K
N
N
850
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P
P
T
T
S
S
C
C
S
S
R
R
R
R
F
F
Y
Y
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860
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L
L
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T
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L
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870
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I
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F
F
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F
880
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D
D
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M
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890
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V
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M
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900
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910
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G
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920
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Key Molecule: Androgen receptor (AR) [3]
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Missense mutation
p.W742C (c.2226G>T)
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
  Metabolic Reprogramming via Altered Pathways (MRAP) Click to Show/Hide
Key Molecule: Squalene epoxidase (SQLE) [2]
Metabolic Type Lipid metabolism
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vivo Model Male NOD/SCID nude mice, With LNCaP, C4-2B, and C4-2B_shSQLE cells Mice
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 Tumor volume assay
Mechanism Description In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide.
References
Ref 1 Protocadherin B9 promotes resistance to bicalutamide and is associated with the survival of prostate cancer patients .Prostate. 2019 Feb;79(2):234-242. doi: 10.1002/pros.23728. Epub 2018 Oct 16. 10.1002/pros.23728
Ref 2 SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer. Onco Targets Ther. 2021 Jul 24;14:4285-4295.
Ref 3 Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndromeCancer Res. 2003 Jan 1;63(1):149-53.

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