Drug Information

Drug (ID: DG01547) and It's Reported Resistant Information
Name
PF-04691502
Synonyms
PF-04691502; 1013101-36-4; PF 04691502; 2-amino-8-((1r,4r)-4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one; PF04691502; UNII-4W39NS61KI; 4W39NS61KI; CHEMBL1234354; PF-4691502; 2-Amino-8-[4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7-one; 2-Amino-8-[trans-4-(2-Hydroxyethoxy)cyclohexyl]-6-(6-Methoxypyridin-3-Yl)-4-Methylpyrido[2,3-D]pyrimidin-7(8h)-One; 2-Amino-8-(cis-4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one; 2-Amino-8-(cis-4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one; 4tv3; MLS006010979; GTPL7936; SCHEMBL1381425; SCHEMBL1381431; SCHEMBL1984896; SCHEMBL10092210; SCHEMBL13976989; EX-A032; QCR-137; HMS3656B21; AOB87714; BCP02895; BDBM50380313; MFCD18782794; NSC760536; NSC800846; s2743; ZINC58660483; AKOS005266645; AKOS030257531; ZINC100015733; ZINC117704832; CCG-268947; CS-0919; DB11974; NSC-760536; NSC-800846; SB20066; NCGC00346659-01; NCGC00381752-02; NCGC00381752-06; AC-28429; AS-17042; HY-15177; SMR004702782; BCP0726000275; PF4691502; SW220185-1; X7464; US8633204, 286; J-000360; PF-04691502, >=98% (HPLC); Q27088316; 2-Amino-8-[trans-4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxy-3-pyridinyl)-4-methyl-pyrido[2,3-d]pyrimidin-7(8H)-one; Pyrido(2,3-d)pyrimidin-7(8H)-one, 2-amino-8-(trans-4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxy-3-pyridinyl)-4-methyl-; trans-2-Amino-8-((1R,4R)-4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one
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Indication
In total 3 Indication(s)
Basal cell carcinoma [ICD-11: 2C32]
Phase 2
[1]
Basal cell nevus syndrome [ICD-11: 2C32]
Phase 2
[1]
Chondrosarcoma [ICD-11: 2B50]
Phase 2
[1]
Structure
Target Hedgehog signaling pathway (HS pathway) NOUNIPROTAC [1]
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Formula
6
IsoSMILES
CC1=C2C=C(C(=O)N(C2=NC(=N1)N)C3CCC(CC3)OCCO)C4=CN=C(C=C4)OC
InChI
InChI=1S/C22H27N5O4/c1-13-17-11-18(14-3-8-19(30-2)24-12-14)21(29)27(20(17)26-22(23)25-13)15-4-6-16(7-5-15)31-10-9-28/h3,8,11-12,15-16,28H,4-7,9-10H2,1-2H3,(H2,23,25,26)
InChIKey
XDLYKKIQACFMJG-UHFFFAOYSA-N
PubChem CID
25033539
TTD Drug ID
D0GD4Q
DrugBank ID
DB11974
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
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
Ovarian cancer [ICD-11: 2C73]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 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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-10
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0
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10
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20
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30
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40
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50
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60
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70
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E
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80
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D
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90
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C
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L
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F
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100
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K
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V
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I
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E
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V
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G
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N
N
R
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E
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110
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E
E
K
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I
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L
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N
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G
F
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120
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A
A
I
I
G
G
M
M
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C
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E
E
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D
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130
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M
M
V
V
K
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D
D
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D
D
F
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140
|
R
R
R
R
N
N
I
I
L
L
N
N
V
V
C
C
K
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E
E
150
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A
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V
D
D
L
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D
D
L
L
N
N
S
S
P
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160
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H
H
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A
A
M
M
Y
Y
V
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Y
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170
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N
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E
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L
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180
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H
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I
Y
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N
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L
L
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G
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190
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I
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I
V
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V
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I
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W
W
V
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I
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200
|
P
P
N
N
N
N
D
D
K
K
Q
Q
K
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Y
Y
T
T
L
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210
|
K
K
I
I
N
N
H
H
D
D
C
C
V
V
P
P
E
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Q
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220
|
V
V
I
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A
A
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K
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T
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230
|
R
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M
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L
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E
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240
|
K
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L
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G
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K
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250
|
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C
C
G
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C
C
D
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260
|
Y
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Y
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270
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Y
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Y
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I
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S
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C
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I
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L
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280
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G
G
R
R
M
M
P
P
N
N
L
L
M
M
L
L
M
M
A
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290
|
K
K
E
E
S
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L
L
Y
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L
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300
|
D
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C
C
F
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Y
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310
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R
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I
I
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T
T
A
A
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Y
Y
M
M
N
N
320
|
G
G
E
E
T
T
S
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T
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K
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S
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L
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W
W
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330
|
I
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N
N
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A
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I
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340
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C
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A
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Y
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N
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N
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350
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D
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360
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G
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G
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370
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N
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N
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380
|
N
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N
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390
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D
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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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N
N
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460
|
G
G
V
V
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T
G
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N
N
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N
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470
|
T
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L
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480
|
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490
|
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N
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500
|
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G
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Y
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510
|
H
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A
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G
L
L
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N
N
R
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L
L
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520
|
D
D
N
N
E
E
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D
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530
|
Q
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L
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540
|
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550
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560
|
T
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L
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570
|
L
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N
N
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R
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580
|
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C
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590
|
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600
|
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L
L
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610
|
M
M
V
V
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G
G
F
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620
|
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K
K
Y
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L
L
T
T
D
D
D
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K
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L
L
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630
|
Q
Q
Y
Y
L
L
I
I
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V
V
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V
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640
|
K
K
Y
Y
E
E
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Q
Y
Y
L
L
D
D
N
N
L
L
L
L
650
|
V
V
R
R
F
F
L
L
L
L
K
K
K
K
A
A
L
L
T
T
660
|
N
N
Q
Q
R
R
I
I
G
G
H
H
F
F
F
F
F
F
W
W
670
|
H
H
L
L
K
K
S
S
E
E
M
M
H
H
N
N
K
K
T
T
680
|
V
V
S
S
Q
Q
R
R
F
F
G
G
L
L
L
L
L
L
E
E
690
|
S
S
Y
Y
C
C
R
R
A
A
C
C
G
G
M
M
Y
Y
L
L
700
|
K
K
H
H
L
L
N
N
R
R
Q
Q
V
V
E
E
A
A
M
M
710
|
E
E
K
K
L
L
I
I
N
N
L
L
T
T
D
D
I
I
L
L
720
|
K
K
Q
Q
E
E
K
K
K
K
D
D
E
E
T
T
Q
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K
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730
|
V
V
Q
Q
M
M
K
K
F
F
L
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V
V
E
E
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Q
M
M
740
|
R
R
R
R
P
P
D
D
F
F
M
M
D
D
A
A
L
L
Q
Q
750
|
G
G
F
F
L
L
S
S
P
P
L
L
N
N
P
P
A
A
H
H
760
|
Q
Q
L
L
G
G
N
N
L
L
R
R
L
L
E
E
E
E
C
C
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 293-MSR cells Fetal kidney Homo sapiens (Human) CVCL_KS18
In Vivo Model Female nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Caspase-Glo 3/7 assay
Mechanism Description The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of PF-04691502 by aberration of the drug's therapeutic target
References
Ref 1 PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activityMol Cancer Ther. 2011 Nov;10(11):2189-99. doi: 10.1158/1535-7163.MCT-11-0185. Epub 2011 Jul 12.

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