Drug Information

Drug (ID: DG01226) and It's Reported Resistant Information
Name
Verteporfin
Synonyms
Visudyne (TN); SCHEMBL6218; Verteporfin (JAN/USP/INN); SCHEMBL1230373; Verteporfin, >=94% (HPLC); HY-B0146; AKOS015896072; AKOS037515819; CS-1950; D01162; Verteporfin, United States Pharmacopeia (USP) Reference Standard
    Click to Show/Hide
Indication
In total 1 Indication(s)
Psoriasis vulgaris [ICD-11: EA90]
Approved
[1]
Structure
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C82H84N8O16
IsoSMILES
CC1=C(C2=CC3=NC(=CC4=C(C(=C(N4)C=C5[C@@]6([C@@H](C(=CC=C6C(=N5)C=C1N2)C(=O)OC)C(=O)OC)C)C)CCC(=O)OC)C(=C3C)CCC(=O)O)C=C.CC1=C(C2=CC3=NC(=CC4=C(C(=C(N4)C=C5[C@@]6([C@@H](C(=CC=C6C(=N5)C=C1N2)C(=O)OC)C(=O)OC)C)C)CCC(=O)O)C(=C3C)CCC(=O)OC)C=C
InChI
1S/2C41H42N4O8/c1-9-23-20(2)29-17-34-27-13-10-26(39(49)52-7)38(40(50)53-8)41(27,5)35(45-34)19-30-22(4)24(11-14-36(46)47)32(44-30)18-33-25(12-15-37(48)51-6)21(3)28(43-33)16-31(23)42-29;1-9-23-20(2)29-17-34-27-13-10-26(39(49)52-7)38(40(50)53-8)41(27,5)35(45-34)19-30-22(4)25(12-15-37(48)51-6)33(44-30)18-32-24(11-14-36(46)47)21(3)28(43-32)16-31(23)42-29/h2*9-10,13,16-19,38,42,44H,1,11-12,14-15H2,2-8H3,(H,46,47)/t2*38-,41+/m00/s1
InChIKey
NJLRKAMQPVVOIU-IDLGWYNRSA-N
PubChem CID
11980904
TTD Drug ID
D0I3XG
DrugBank ID
DB00460
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
Prostate cancer [ICD-11: 2C82]
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: Transcriptional coactivator YAP1 (YAP1) [1]
Sensitive Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Expression
Down-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: 7.45E-03
Fold-change: -4.71E-02
Z-score: -2.78E+00
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEp-2 cells Skin Homo sapiens (Human) CVCL_1906
U251 cells Brain Homo sapiens (Human) CVCL_0021
BT474 cells Breast Homo sapiens (Human) CVCL_0179
A172 cells Brain Homo sapiens (Human) CVCL_0131
U87 cells Brain Homo sapiens (Human) CVCL_0022
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Calu-3 cells Lung Homo sapiens (Human) CVCL_0609
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
In Vivo Model Male BALB/c nude mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; qRT-PCR
Experiment for
Drug Resistance		 WST-1 assay; Colony formation assay; Annexin V-FITC/PI Apoptosis assay
Mechanism Description MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells.
Key Molecule: Myb-related protein B (MYBL2) [1]
Sensitive Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Molecule Alteration Expression
Down-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: 3.51E-02
Fold-change: -9.80E-02
Z-score: -2.22E+00
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEp-2 cells Skin Homo sapiens (Human) CVCL_1906
U251 cells Brain Homo sapiens (Human) CVCL_0021
BT474 cells Breast Homo sapiens (Human) CVCL_0179
A172 cells Brain Homo sapiens (Human) CVCL_0131
U87 cells Brain Homo sapiens (Human) CVCL_0022
H1299 cells Lung Homo sapiens (Human) CVCL_0060
Calu-3 cells Lung Homo sapiens (Human) CVCL_0609
HuTu80 cells Small intestine Homo sapiens (Human) CVCL_1301
In Vivo Model Male BALB/c nude mouse model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; qRT-PCR
Experiment for
Drug Resistance		 WST-1 assay; Colony formation assay; Annexin V-FITC/PI Apoptosis assay
Mechanism Description MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells.
Uveal melanoma [ICD-11: 2D0Y]
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: Guanine nucleotide-binding protein alpha-q (GNAQ) [2]
Sensitive Disease Uveal melanoma [ICD-11: 2D0Y.0]
 Disease Info 
Molecule Alteration Missense mutation
p.Q209L (c.626A>T)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.50  Å
PDB: 6VU5
Mutant Type Structure Method: Electron microscopy Resolution: 2.90  Å
PDB: 7F6G
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.91
TM score: 0.72705
Amino acid change:
Q209L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
H
-
H
-
H
-
H
-
H
-
H
-
H
-
H
0
|
-
H
M
H
T
T
L
L
E
E
S
S
I
I
M
M
A
A
C
C
10
|
C
C
L
L
S
S
E
E
E
E
A
A
K
K
E
E
A
A
R
R
20
|
R
R
I
I
N
N
D
D
E
E
I
I
E
E
R
R
Q
Q
L
L
30
|
R
R
R
R
D
D
K
K
R
R
D
D
A
A
R
R
R
R
E
E
40
|
L
L
K
K
L
L
L
L
L
L
L
L
G
G
T
T
G
G
E
E
50
|
S
S
G
G
K
K
S
S
T
T
F
F
I
I
K
K
Q
Q
M
M
60
|
R
R
I
I
I
I
H
H
G
G
S
S
G
G
Y
Y
S
S
D
D
70
|
E
E
D
D
K
K
R
R
G
G
F
F
T
T
K
K
L
L
V
V
80
|
Y
Y
Q
Q
N
N
I
I
F
F
T
T
A
A
M
M
Q
Q
A
A
90
|
M
M
I
I
R
R
A
A
M
M
D
D
T
T
L
L
K
K
I
I
100
|
P
P
Y
Y
K
K
Y
Y
E
E
H
H
N
N
K
K
A
A
H
H
110
|
A
A
Q
Q
L
L
V
V
R
R
E
E
V
V
D
D
V
V
E
E
120
|
K
K
V
V
S
S
A
A
F
F
E
E
N
N
P
P
Y
Y
V
V
130
|
D
D
A
A
I
I
K
K
S
S
L
L
W
W
N
N
D
D
P
P
140
|
G
G
I
I
Q
Q
E
E
C
C
Y
Y
D
D
R
R
R
R
R
R
150
|
E
E
Y
Y
Q
Q
L
L
S
S
D
D
S
S
T
T
K
K
Y
Y
160
|
Y
Y
L
L
N
N
D
D
L
L
D
D
R
R
V
V
A
A
D
D
170
|
P
P
A
A
Y
Y
L
L
P
P
T
T
Q
Q
Q
Q
D
D
V
V
180
|
L
L
R
R
V
V
R
Q
V
V
P
P
T
T
T
T
G
G
I
I
190
|
I
I
E
E
Y
Y
P
P
F
F
D
D
L
L
Q
Q
S
S
V
V
200
|
I
I
F
F
R
R
M
M
V
V
D
D
V
V
G
G
G
G
Q
L
210
|
R
R
S
S
E
E
R
R
R
R
K
K
W
W
I
I
H
H
C
C
220
|
F
F
E
E
N
N
V
V
T
T
S
S
I
I
M
M
F
F
L
L
230
|
V
V
A
A
L
L
S
S
E
E
Y
Y
D
D
Q
Q
V
V
L
L
240
|
V
V
E
E
S
S
D
D
N
N
E
E
N
N
R
R
M
M
E
E
250
|
E
E
S
S
K
K
A
A
L
L
F
F
R
R
T
T
I
I
I
I
260
|
T
T
Y
Y
P
P
W
W
F
F
Q
Q
N
N
S
S
S
S
V
V
270
|
I
I
L
L
F
F
L
L
N
N
K
K
K
K
D
D
L
L
L
L
280
|
E
E
E
E
K
K
I
I
M
M
Y
Y
S
S
H
H
L
L
V
V
290
|
D
D
Y
Y
F
F
P
P
E
E
Y
Y
D
D
G
G
P
P
Q
Q
300
|
R
R
D
D
A
A
Q
Q
A
A
A
A
R
R
E
E
F
F
I
I
310
|
L
L
K
K
M
M
F
F
V
V
D
D
L
L
N
N
P
P
D
D
320
|
S
S
D
D
K
K
I
I
I
I
Y
Y
S
S
H
H
F
F
T
T
330
|
C
C
A
A
T
T
D
D
T
T
E
E
N
N
I
I
R
R
F
F
340
|
V
V
F
F
A
A
A
A
V
V
K
K
D
D
T
T
I
I
L
L
350
|
Q
Q
L
L
N
N
L
L
K
K
E
E
Y
Y
N
N
L
L
V
V
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Hippo signaling pathway Inhibition hsa04390
In Vivo Model Nude mouse PDX model Mus musculus
References
Ref 1 MYBL2 disrupts the Hippo-YAP pathway and confers castration resistance and metastatic potential in prostate cancer .Theranostics. 2021 Mar 31;11(12):5794-5812. doi: 10.7150/thno.56604. eCollection 2021. 10.7150/thno.56604
Ref 2 YAP inhibition blocks uveal melanogenesis driven by GNAQ or GNA11 mutationsMol Cell Oncol. 2014 Dec 1;2(1):e970957. doi: 10.4161/23723548.2014.970957. eCollection 2015 Jan-Mar.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Yu.