Drug Information

Drug (ID: DG01545) and It's Reported Resistant Information
Name
MK-2206
Synonyms
MK-2206; 1032349-93-1; UNII-51HZG6MP1K; MK 2206; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one; MK2206; 51HZG6MP1K; CHEMBL1079175; CHEBI:67271; NCGC00186465-01; DSSTox_CID_28874; DSSTox_RID_83143; DSSTox_GSID_48948; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one; 1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one, 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-;1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one, 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-;8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-ol; 8-(4-(1-Aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthy ridin-3(2H)-one; 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3(2H)-one; CAS-1032350-13-2; 1032349-77-1; MK-2206 free base; SCHEMBL530721; GTPL7945; DTXSID3048948; BCP20200; Tox21_113368; BDBM50313650; NSC756656; NSC800794; ZINC36382821; AKOS032945686; Tox21_113368_1; BCP9000938; MK 2206;MK2206; NSC-756656; NSC-800794; SB16805; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one; NCGC00186465-02; NCGC00186465-03; NCGC00186465-04; NCGC00186465-08; DB-058959; FT-0738942; A25240; MK2206;MK 2206;MK-2206 dihydrochloride; cas:1032350-13-2;MK 2206; BRD-K68065987-300-02-6; Q25100065; 1,2,4-Triazolo(3,4-f)(1,6)naphthyridin-3(2H)-one, 8-(4-(1-aminocyclobutyl)phenyl)-9-phenyl-; 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl-1,2,4-triazolo[3,4-f][1,6]naphthyridin-3(2H)-one dihydrochloride;MK-2206 Dihydrochloride; 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-3(2H)-one
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Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 2
[1]
Structure
Target MAPK/ERK kinase kinase (MAP3K) NOUNIPROTAC [2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
3
IsoSMILES
C1CC(C1)(C2=CC=C(C=C2)C3=C(C=C4C(=N3)C=CN5C4=NNC5=O)C6=CC=CC=C6)N
InChI
InChI=1S/C25H21N5O/c26-25(12-4-13-25)18-9-7-17(8-10-18)22-19(16-5-2-1-3-6-16)15-20-21(27-22)11-14-30-23(20)28-29-24(30)31/h1-3,5-11,14-15H,4,12-13,26H2,(H,29,31)
InChIKey
ULDXWLCXEDXJGE-UHFFFAOYSA-N
PubChem CID
24964624
ChEBI ID
CHEBI:67271
TTD Drug ID
D0I3RD
Type(s) of Resistant Mechanism of This Drug
  RTDM: Regulation by the Disease Microenvironment
  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
Pancreatic cancer [ICD-11: 2C10]
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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: GTPase KRas (KRAS) [2]
Sensitive Disease Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G12D (c.35G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.40  Å
PDB: 6VJJ
Mutant Type Structure Method: X-ray diffraction Resolution: 2.10  Å
PDB: 8JHL
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.55
TM score: 0.9318
Amino acid change:
G12D
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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0
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G
-
M
M
T
T
E
E
Y
Y
K
K
L
L
V
V
V
V
V
V
10
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G
G
A
A
G
D
G
G
V
V
G
G
K
K
S
S
A
A
L
L
20
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T
T
I
I
Q
Q
L
L
I
I
Q
Q
N
N
H
H
F
F
V
V
30
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D
D
E
E
Y
Y
D
D
P
P
T
T
I
I
E
E
D
D
S
S
40
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Y
Y
R
R
K
K
Q
Q
V
V
V
V
I
I
D
D
G
G
E
E
50
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T
T
C
C
L
L
L
L
D
D
I
I
L
L
D
D
T
T
A
A
60
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G
G
Q
Q
E
E
E
E
Y
Y
S
S
A
A
M
M
R
R
D
D
70
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Q
Q
Y
Y
M
M
R
R
T
T
G
G
E
E
G
G
F
F
L
L
80
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C
C
V
V
F
F
A
A
I
I
N
N
N
N
T
T
K
K
S
S
90
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F
F
E
E
D
D
I
I
H
H
H
H
Y
Y
R
R
E
E
Q
Q
100
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I
I
K
K
R
R
V
V
K
K
D
D
S
S
E
E
D
D
V
V
110
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P
P
M
M
V
V
L
L
V
V
G
G
N
N
K
K
C
C
D
D
120
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L
L
P
P
S
S
R
R
T
T
V
V
D
D
T
T
K
K
Q
Q
130
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A
A
Q
Q
D
D
L
L
A
A
R
R
S
S
Y
Y
G
G
I
I
140
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P
P
F
F
I
I
E
E
T
T
S
S
A
A
K
K
T
T
R
R
150
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Q
Q
G
R
V
V
D
E
D
D
A
A
F
F
Y
Y
T
T
L
L
160
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V
V
R
R
E
E
I
I
R
R
K
Q
H
Y
K
R
E
L
K
K
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The missense mutation p.G12D (c.35G>A) in gene KRAS cause the sensitivity of MK-2206 by unusual activation of pro-survival pathway
Breast cancer [ICD-11: 2C60]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA) [1]
Sensitive Disease Breast adenocarcinoma [ICD-11: 2C60.1]
 Disease Info 
Molecule Alteration Missense mutation
p.E545K (c.1633G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Soft-agar colony formation assay
Mechanism Description The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of MK-2206 by aberration of the drug's therapeutic target
References
Ref 1 PIK3CA and AKT1 mutations have distinct effects on sensitivity to targeted pathway inhibitors in an isogenic luminal breast cancer model systemClin Cancer Res. 2013 Oct 1;19(19):5413-22. doi: 10.1158/1078-0432.CCR-13-0884. Epub 2013 Jul 25.
Ref 2 First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumorsJ Clin Oncol. 2011 Dec 10;29(35):4688-95. doi: 10.1200/JCO.2011.35.5263. Epub 2011 Oct 24.

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