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Details

Stereochemistry ACHIRAL
Molecular Formula C25H21N5O
Molecular Weight 407.4671
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MK-2206 FREE BASE

SMILES

NC1(CCC1)C2=CC=C(C=C2)C3=NC4=C(C=C3C5=CC=CC=C5)C6=NNC(=O)N6C=C4

InChI

InChIKey=ULDXWLCXEDXJGE-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C25H21N5O
Molecular Weight 407.4671
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800028810 | http://www.pharmacodia.com/yaodu/html/v1/chemicals/cddaa6e1ad5ba4c70c6c05db38099fa0.html | https://en.wikipedia.org/wiki/MK-2206 | https://www.ncbi.nlm.nih.gov/pubmed/20571069

MK-2206 is an oral selective allosteric inhibitor of Akt that targets all three isoforms of human Akt (Akt-1, Akt-2 and Akt-3). In a phase I study of solid tumors, MK-2206 demonstrated evidence of target modulation and anti-proliferative activity as a single agent and in combination with other agents. Current ongoing trials of MK-2206 include monotherapy and combination therapy in breast cancer, colorectal cancer, haematological malignancies, non-small cell lung cancer and other. Detected treatment-related adverse event are: rash, fatigue, hyperglycemia.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
264 nM
200 mg 1 times / week single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
345 nM
200 mg 1 times / week multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
466 nM
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
66.4 nM
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
132 nM
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
163 nM
60 mg 1 times / 2 days multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
232 nM
90 mg 1 times / 2 days multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
16400 nM × h
200 mg 1 times / week single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
23500 nM × h
200 mg 1 times / week multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
27700 nM × h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1820 nM × h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3950 nM × h
90 mg single, oral
dose: 90 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5860 nM × h
60 mg 1 times / 2 days multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7970 nM × h
90 mg 1 times / 2 days multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
75.1 h
200 mg 1 times / week multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
71.3 h
60 mg 1 times / 2 days multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
66.2 h
90 mg 1 times / 2 days multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MK-2206 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
300 mg 1 times / week multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / week
Route: oral
Route: multiple
Dose: 300 mg, 1 times / week
Sources: Page: p.5, 25
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 3
Sources: Page: p.5, 25
DLT: Skin rash...
Dose limiting toxicities:
Skin rash (grade 3, 100%)
Sources: Page: p.5, 25
200 mg 1 times / week multiple, oral
MTD
Dose: 200 mg, 1 times / week
Route: oral
Route: multiple
Dose: 200 mg, 1 times / week
Sources: Page: p.5, 25
unhealthy, ADULT
n = 17
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 17
Sources: Page: p.5, 25
DLT: Skin rash, Dermatitis acneiform...
Dose limiting toxicities:
Skin rash (grade 3, 17.6%)
Dermatitis acneiform (grade 3, 5.9%)
Sources: Page: p.5, 25
60 mg 1 times / 2 days multiple, oral
MTD
Dose: 60 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 60 mg, 1 times / 2 days
Sources: Page: p.4690
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 20
Sources: Page: p.4690
DLT: Erythematous rash...
Dose limiting toxicities:
Erythematous rash (grade 3, 5%)
Sources: Page: p.4690
60 mg 1 times / 2 days multiple, oral
MTD
Dose: 60 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 60 mg, 1 times / 2 days
Sources: Page: sup. table1
unhealthy, ADULT
n = 38
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 38
Sources: Page: sup. table1
DLT: Stomatitis, Skin rash...
Dose limiting toxicities:
Stomatitis (grade 3, 2.6%)
Skin rash (grade 3, 2.6%)
Skin rash (grade 3, 18.4%)
Skin rash (grade 3, 5.3%)
Sources: Page: sup. table1
90 mg 1 times / 2 days multiple, oral
Studied dose
Dose: 90 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 90 mg, 1 times / 2 days
Sources: Page: p.4690
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.4690
DLT: Stomatitis, Erythematous rash...
Dose limiting toxicities:
Stomatitis (grade 3, 14.3%)
Erythematous rash (grade 3-4, 57.1%)
Sources: Page: p.4690
AEs

AEs

AESignificanceDosePopulation
Skin rash grade 3, 100%
DLT
300 mg 1 times / week multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / week
Route: oral
Route: multiple
Dose: 300 mg, 1 times / week
Sources: Page: p.5, 25
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 3
Sources: Page: p.5, 25
Skin rash grade 3, 17.6%
DLT
200 mg 1 times / week multiple, oral
MTD
Dose: 200 mg, 1 times / week
Route: oral
Route: multiple
Dose: 200 mg, 1 times / week
Sources: Page: p.5, 25
unhealthy, ADULT
n = 17
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 17
Sources: Page: p.5, 25
Dermatitis acneiform grade 3, 5.9%
DLT
200 mg 1 times / week multiple, oral
MTD
Dose: 200 mg, 1 times / week
Route: oral
Route: multiple
Dose: 200 mg, 1 times / week
Sources: Page: p.5, 25
unhealthy, ADULT
n = 17
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 17
Sources: Page: p.5, 25
Erythematous rash grade 3, 5%
DLT
60 mg 1 times / 2 days multiple, oral
MTD
Dose: 60 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 60 mg, 1 times / 2 days
Sources: Page: p.4690
unhealthy, ADULT
n = 20
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 20
Sources: Page: p.4690
Skin rash grade 3, 18.4%
DLT, Disc. AE
60 mg 1 times / 2 days multiple, oral
MTD
Dose: 60 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 60 mg, 1 times / 2 days
Sources: Page: sup. table1
unhealthy, ADULT
n = 38
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 38
Sources: Page: sup. table1
Stomatitis grade 3, 2.6%
DLT
60 mg 1 times / 2 days multiple, oral
MTD
Dose: 60 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 60 mg, 1 times / 2 days
Sources: Page: sup. table1
unhealthy, ADULT
n = 38
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 38
Sources: Page: sup. table1
Skin rash grade 3, 2.6%
DLT, Disc. AE
60 mg 1 times / 2 days multiple, oral
MTD
Dose: 60 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 60 mg, 1 times / 2 days
Sources: Page: sup. table1
unhealthy, ADULT
n = 38
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 38
Sources: Page: sup. table1
Skin rash grade 3, 5.3%
DLT
60 mg 1 times / 2 days multiple, oral
MTD
Dose: 60 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 60 mg, 1 times / 2 days
Sources: Page: sup. table1
unhealthy, ADULT
n = 38
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 38
Sources: Page: sup. table1
Stomatitis grade 3, 14.3%
DLT
90 mg 1 times / 2 days multiple, oral
Studied dose
Dose: 90 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 90 mg, 1 times / 2 days
Sources: Page: p.4690
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.4690
Erythematous rash grade 3-4, 57.1%
DLT
90 mg 1 times / 2 days multiple, oral
Studied dose
Dose: 90 mg, 1 times / 2 days
Route: oral
Route: multiple
Dose: 90 mg, 1 times / 2 days
Sources: Page: p.4690
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 7
Sources: Page: p.4690
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
PubMed

PubMed

TitleDatePubMed
MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo.
2010 Jul
The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway.
2011 Apr
Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels.
2012 Aug
Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice.
2012 Oct
Detection of key enzymes, free radical reaction products and activated signaling molecules as biomarkers of cell damage induced by benzo[a]pyrene in human keratinocytes.
2014 Aug
PI3K signaling mediates diverse regulation of ATF4 expression for the survival of HK-2 cells exposed to cadmium.
2014 Feb
Effects of AKT inhibition on HGF-mediated erlotinib resistance in non-small cell lung cancer cell lines.
2015 Apr
Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line.
2015 Dec 25
The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells.
2015 Jan
Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.
2015 Jan 5
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.
2015 Jun
S6 inhibition contributes to isoflurane neurotoxicity in the developing brain.
2015 Mar 4
Patents

Sample Use Guides

90 mg weekly (1st 28 days cycle); 135 mg weekly (2nd 28 days cycle)
Route of Administration: Oral
MK-2206 alone more potently inhibited the cell growth of Ras wild-type (WT) cell lines (A431, HCC827, and NCI-H292; IC50s of 5.5, 4.3, and 5.2 μmol/L, respectively) as compared with Ras-mutant cell lines (NCI-H358, NCI-H23, NCI-H1299, and Calu-6; IC50s of 13.5, 14.1, 27.0, and 28.6 μmol/L, respectively), with the exception of NCI-H460, which has a PIK3CA E545K mutation (IC50, 3.4 μmol/L).
Substance Class Chemical
Created
by admin
on Sat Dec 16 06:50:16 GMT 2023
Edited
by admin
on Sat Dec 16 06:50:16 GMT 2023
Record UNII
51HZG6MP1K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MK-2206 FREE BASE
Common Name English
1,2,4-TRIAZOLO(3,4-F)(1,6)NAPHTHYRIDIN-3(2H)-ONE, 8-(4-(1-AMINOCYCLOBUTYL)PHENYL)-9-PHENYL-
Systematic Name English
8-(4-(1-AMINOCYCLOBUTYL)PHENYL)-9-PHENYL-1,2,4-TRIAZOLO(3,4-F)(1,6)NAPHTHYRIDIN-3(2H)-ONE
Systematic Name English
Code System Code Type Description
PUBCHEM
24964624
Created by admin on Sat Dec 16 06:50:16 GMT 2023 , Edited by admin on Sat Dec 16 06:50:16 GMT 2023
PRIMARY
FDA UNII
51HZG6MP1K
Created by admin on Sat Dec 16 06:50:16 GMT 2023 , Edited by admin on Sat Dec 16 06:50:16 GMT 2023
PRIMARY
CAS
1032349-93-1
Created by admin on Sat Dec 16 06:50:16 GMT 2023 , Edited by admin on Sat Dec 16 06:50:16 GMT 2023
PRIMARY
WIKIPEDIA
MK-2206
Created by admin on Sat Dec 16 06:50:16 GMT 2023 , Edited by admin on Sat Dec 16 06:50:16 GMT 2023
PRIMARY
NCI_THESAURUS
C90581
Created by admin on Sat Dec 16 06:50:16 GMT 2023 , Edited by admin on Sat Dec 16 06:50:16 GMT 2023
PRIMARY
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