Drug Information

Drug (ID: DG01474) and It's Reported Resistant Information
Name
Perifosine
Synonyms
Perifosine; 157716-52-4; KRX-0401; 1,1-Dimethylpiperidin-1-ium-4-yl octadecyl phosphate; (1,1-dimethylpiperidin-1-ium-4-yl) octadecyl phosphate; Perifosine (KRX-0401); NSC 639966; D 21266; 1,1-dimethylpiperidinium-4-yl octadecyl phosphate; UNII-2GWV496552; KRX 0401; NSC639966; D-21266; NSC-639966; CHEBI:67272; 2GWV496552; NCGC00187909-01; Piperidinium, 4-[[hydroxy(octadecyloxy)phosphinyl]oxy]-1,1-dimethyl-, inner salt; 1,1-dimethylpiperidin-1-ium-4-yl octadecyl phosphate.; Piperidinium, 4-((hydroxy(octadecyloxy)phosphinyl)oxy)-1,1-dimethyl-, inner salt; Perifosine [INN]; NKA17; C25H52NO4P; octadecyl-(1,1-dimethyl-4-piperidylio)phosphate; 4-((Hydroxy(octadecyloxy)phosphinyl)oxy)-1,1-dimethylpiperidinium inner salt; DSSTox_CID_28872; DSSTox_RID_83141; DSSTox_GSID_48946; SCHEMBL93872; CHEMBL372764; GTPL7424; DTXSID3048946; AOB3006; QCR-270; BCP00245; EX-A2229; YHI-1003; Tox21_113365; BDBM50431630; MFCD00927554; NSC800842; s1037; Piperidinium,1-dimethyl-, inner salt; AKOS005146344; CCG-269358; CS-0209; DB06641; EX-3388; GS-3834; NSC-800842; NCGC00187909-02; NCGC00187909-13; AC-25019; AM808092; HY-50909; CAS-157716-52-4; FT-0651459; W3423; A23834; D21266; Octadecyl-(1,1-dimethyl-4-piperidylio) phosphate; J-500086; Q3411917; Perifosine; KRX-0401; NSC 639966; D21266; 4-Hydroxy-1,1-dimethylpiperidinium hydroxide, octadecyl hydrogen phosphate, inner salt
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Indication
In total 3 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 1
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Breast cancer [ICD-11: 2C60]
[2]
Target Tubulin (TUB) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
20
IsoSMILES
CCCCCCCCCCCCCCCCCCOP(=O)([O-])OC1CC[N+](CC1)(C)C
InChI
InChI=1S/C25H52NO4P/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-24-29-31(27,28)30-25-20-22-26(2,3)23-21-25/h25H,4-24H2,1-3H3
InChIKey
SZFPYBIJACMNJV-UHFFFAOYSA-N
PubChem CID
148177
ChEBI ID
CHEBI:67272
TTD Drug ID
D0O5WP
DrugBank ID
DB06641
Type(s) of Resistant Mechanism of This Drug
  IDUE: Irregularity in Drug Uptake and Drug Efflux
  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
Oral squamous cell carcinoma [ICD-11: 2B6E]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Sensitive Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KBV20C cells Oral epithelium Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 Cell viability assay
Mechanism Description Perifosine increased cytotoxicity in P-gp-overexpressing drug-resistant KBV20C cancer cells
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Sensitive Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KBV20C cells Oral epithelium Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 Microscopic assay
Mechanism Description Perifosine increased cytotoxicity in P-gp-overexpressing drug-resistant KBV20C cancer cells
Breast cancer [ICD-11: 2C60]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Resistant Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Drug Resistance		 Annexin V assay
Mechanism Description Perifosine afforded highly selective sensitization effects only in drug-resistant MCF-8/ADR cancer cells
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7/ADR cells Breast Homo sapiens (Human) N.A.
Experiment for
Drug Resistance		 Annexin V assay
Mechanism Description Perifosine afforded highly selective sensitization effects only in drug-resistant MCF-7/ADR cancer cells
Thyroid cancer [ICD-11: 2D10]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.H1047R (c.3140A>G)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 2.41  Å
PDB: 8DCP
Mutant Type Structure Method: X-ray diffraction Resolution: 2.61  Å
PDB: 8V8V
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.09
TM score: 0.95656
Amino acid change:
H1047R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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80
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90
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100
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110
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120
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130
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140
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150
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160
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170
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180
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190
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200
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210
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220
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230
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240
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250
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260
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270
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280
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290
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300
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310
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320
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340
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370
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380
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390
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400
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410
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420
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430
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440
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450
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460
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470
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480
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490
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500
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510
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520
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530
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540
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560
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570
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580
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590
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600
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610
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620
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630
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640
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650
|
V
V
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L
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660
|
N
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670
|
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N
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680
|
V
V
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690
|
S
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Y
Y
C
C
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700
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K
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710
|
E
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L
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N
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720
|
K
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E
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730
|
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740
|
R
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D
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A
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L
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750
|
G
G
F
F
L
L
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L
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N
N
P
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A
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760
|
Q
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L
L
G
G
N
N
L
L
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L
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770
|
R
R
I
I
M
M
S
S
S
S
A
A
K
K
R
R
P
P
L
L
780
|
W
W
L
L
N
N
W
W
E
E
N
N
P
P
D
D
I
I
M
M
790
|
S
S
E
E
L
L
L
L
F
F
Q
Q
N
N
N
N
E
E
I
I
800
|
I
I
F
F
K
K
N
N
G
G
D
D
D
D
L
L
R
R
Q
Q
810
|
D
D
M
M
L
L
T
T
L
L
Q
Q
I
I
I
I
R
R
I
I
820
|
M
M
E
E
N
N
I
I
W
W
Q
Q
N
N
Q
Q
G
G
L
L
830
|
D
D
L
L
R
R
M
M
L
L
P
P
Y
Y
G
G
C
C
L
L
840
|
S
S
I
I
G
G
D
D
C
C
V
V
G
G
L
L
I
I
E
E
850
|
V
V
V
V
R
R
N
N
S
S
H
H
T
T
I
I
M
M
Q
Q
860
|
I
I
Q
Q
C
C
K
K
G
G
G
G
L
L
K
K
G
G
A
A
870
|
L
L
Q
Q
F
F
N
N
S
S
H
H
T
T
L
L
H
H
Q
Q
880
|
W
W
L
L
K
K
D
D
K
K
N
N
K
K
G
G
E
E
I
I
890
|
Y
Y
D
D
A
A
A
A
I
I
D
D
L
L
F
F
T
T
R
R
900
|
S
S
C
C
A
A
G
G
Y
Y
C
C
V
V
A
A
T
T
F
F
910
|
I
I
L
L
G
G
I
I
G
G
D
D
R
R
H
H
N
N
S
S
920
|
N
N
I
I
M
M
V
V
K
K
D
D
D
D
G
G
Q
Q
L
L
930
|
F
F
H
H
I
I
D
D
F
F
G
G
H
H
F
F
L
L
D
D
940
|
H
H
K
K
K
K
K
K
K
K
F
F
G
G
Y
Y
K
K
R
R
950
|
E
E
R
R
V
V
P
P
F
F
V
V
L
L
T
T
Q
Q
D
D
960
|
F
F
L
L
I
I
V
V
I
I
S
S
K
K
G
G
A
A
Q
Q
970
|
E
E
C
C
T
T
K
K
T
T
R
R
E
E
F
F
E
E
R
R
980
|
F
F
Q
Q
E
E
M
M
C
C
Y
Y
K
K
A
A
Y
Y
L
L
990
|
A
A
I
I
R
R
Q
Q
H
H
A
A
N
N
L
L
F
F
I
I
1000
|
N
N
L
L
F
F
S
S
M
M
M
M
L
L
G
G
S
S
G
G
1010
|
M
M
P
P
E
E
L
L
Q
Q
S
S
F
F
D
D
D
D
I
I
1020
|
A
A
Y
Y
I
I
R
R
K
K
T
T
L
L
A
A
L
L
D
D
1030
|
K
K
T
T
E
E
Q
Q
E
E
A
A
L
L
E
E
Y
Y
F
F
1040
|
M
M
K
K
Q
Q
M
M
N
N
D
D
A
A
H
R
H
H
G
G
1050
|
G
G
W
W
T
T
T
T
K
K
M
M
D
D
W
W
I
I
F
F
1060
|
H
H
T
T
I
I
K
K
Q
Q
H
H
A
A
L
L
N
N
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of Perifosine by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.E542K (c.1624G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The missense mutation p.E542K (c.1624G>A) in gene PIK3CA cause the sensitivity of Perifosine by unusual activation of pro-survival pathway
Key Molecule: Phosphatase and tensin homolog (PTEN) [1]
Sensitive Disease Thyroid gland cancer [ICD-11: 2D10.0]
 Disease Info 
Molecule Alteration Nonsense
p.R130* (c.388C>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
C643 cells Thyroid gland Homo sapiens (Human) CVCL_5969
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
SW1736 cells Thyroid Homo sapiens (Human) CVCL_3883
HTH7 cells Thyroid gland Homo sapiens (Human) CVCL_6289
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
Hth74 cells Thyroid gland Homo sapiens (Human) CVCL_6288
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The nonsense p.R130* (c.388C>T) in gene PTEN cause the sensitivity of Perifosine by unusual activation of pro-survival pathway.
References
Ref 1 Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycinCancer Res. 2009 Sep 15;69(18):7311-9. doi: 10.1158/0008-5472.CAN-09-1077. Epub 2009 Aug 25.
Ref 2 Low-Dose Perifosine, a Phase II Phospholipid Akt Inhibitor, Selectively Sensitizes Drug-Resistant ABCB1-Overexpressing Cancer Cells. Biomol Ther (Seoul). 2025 Jan 1;33(1):170-181.

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