Page 80 - 《中国药科大学学报》2026年第1期

74 学报 Journal of China Pharmaceutical University 2026, 57(1): 68 − 77 第 57 卷

A B
Marker DMSO Penfluridol DMSO 30 min Penfluridol 30 min DMSO 35 min Penfluridol 35 min Marker
kD
135
120
100
70
50
134 694 269
40
30
DMSO Penfluridol
25
14

C D Overall survival in E
Gene symbol Sequest high throughput skin cutaneous melanoma Penfluridol
HSPA6 55.75 1.0 Low HSPA6 Group
EZR 31.16 High HSPA6 Group
Logrank P=0.0099
PPP2CB 27.63 0.8 HR(high)=0.71
P(HR)=0.011
PPP2R1B 26.98 n(high)=229
n(low)=229
HSPA1B 23.26 0.6
GDI1 18.58 Percent survival
ACTR1B 17.84 0.4
DDX17 15.49
LCP1 13.22 0.2
VCL 12.19
CCT... 11.64 0 HSPA6
200
… 10.47 0 100 t/month 300
ASP201
F G SER ARG TYR ASP
GLY340 ARG344 A:277 A:274 A:17 A:368
F ASP
GLU177 ASP368 SER277 ARG N H A:201
A:344 O
LYS273
LYS
ASP12 LYS A:73
A:273 F
GLY204 ARQ274 Cl
THR F
TYR17 GLU233 A:16 F GLU
A:177
GLU ASP
LYS73 THR16 A:233 GLY GLY A:12
A:340 A:204
H Penfluridol I
80 Affinity K D : 5.58×10 mol/L 120 Penfluridol 50 μmol/L
−6
25 μmol/L
100 12.5 μmol/L
70 80 6.25 μmol/L
Response/RU 60 Response/RU 60 1.56 μmol/L
3.13 μmol/L
0.78 μmol/L
50
40
40 20
30 0
0 20 40 60 0 50 100 150
c(Penfluridol)/(μmol/L) t/s
Figure 4 Targeted binding of penfluridol to HSPA6
A: Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and stained using coomassie brilliant blue
staining; B: Venn diagram; C: Differential protein scores: mass spectrometry scores of the top 10 differentially expressed proteins are listed; D:
Kaplan-Meier survival curve: skin cutaneous melanoma (SKCM) patients with high HSPA6 expression (red) exhibited significantly better prognosis
than those with low expression (blue); E: Surface representation of the docked structure; F: 3D interaction diagram between protein HSPA6 and
the small molecule penfluridol (Yellow circles indicate hydrogen bond positions); G: 2D interaction diagram between protein HSPA6 and the small
molecule penfluridol (Black circles indicate hydrogen bond positions); H: Saturation binding curve; I: Real-time binding kinetics curve