MK-2206 FREE BASE

Investigational

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

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

Description

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase AKT 31	Negative Allosteric Modulator 43	5.0 nM [IC50]
Serine/threonine-protein kinase AKT2 17	Negative Allosteric Modulator 43	12.0 nM [IC50]
Serine/threonine-protein kinase AKT3 17	Negative Allosteric Modulator 43	65.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 432	Primary	Phase II 1,147	Unknown
Adenoid cystic carcinoma 6	Primary	Phase II 1,147	Unknown
Colorectal cancer 102	Primary	Phase II 1,147	Unknown

C_max

Value	Dose	Analyte	Population
66.4 nM	60 mg single, oral	MK-2206 plasma	Homo sapiens
232 nM	90 mg 1 times / 2 days multiple, oral	MK-2206 plasma	Homo sapiens
163 nM	60 mg 1 times / 2 days multiple, oral	MK-2206 plasma	Homo sapiens
132 nM	90 mg single, oral	MK-2206 plasma	Homo sapiens
345 nM	200 mg 1 times / week multiple, oral	MK-2206 plasma	Homo sapiens
466 nM	300 mg single, oral	MK-2206 plasma	Homo sapiens
264 nM	200 mg single, oral	MK-2206 plasma	Homo sapiens
95.9 nM	60 mg single, oral	MK-2206 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
1820 nM × h	60 mg single, oral	MK-2206 plasma	Homo sapiens
7970 nM × h	90 mg 1 times / 2 days multiple, oral	MK-2206 plasma	Homo sapiens
5860 nM × h	60 mg 1 times / 2 days multiple, oral	MK-2206 plasma	Homo sapiens
3950 nM × h	90 mg single, oral	MK-2206 plasma	Homo sapiens
23500 nM × h	200 mg 1 times / week multiple, oral	MK-2206 plasma	Homo sapiens
27700 nM × h	300 mg single, oral	MK-2206 plasma	Homo sapiens
16400 nM × h	200 mg single, oral	MK-2206 plasma	Homo sapiens
2720 nM × h	60 mg single, oral	MK-2206 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
66.2 h	90 mg 1 times / 2 days multiple, oral	MK-2206 plasma	Homo sapiens
71.3 h	60 mg 1 times / 2 days multiple, oral	MK-2206 plasma	Homo sapiens
75.1 h	200 mg 1 times / week multiple, oral	MK-2206 plasma	Homo sapiens
71.8 h	60 mg single, oral	MK-2206 plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
300 mg 1 times / week multiple, oral Highest studied dose	unhealthy, ADULT	DLT: Skin rash...
200 mg 1 times / week multiple, oral MTD	unhealthy, ADULT	DLT: Skin rash, Dermatitis acneiform...
60 mg 1 times / 2 days multiple, oral MTD	unhealthy, ADULT	DLT: Erythematous rash...
60 mg 1 times / 2 days multiple, oral MTD	unhealthy, ADULT	DLT: Skin rash, Stomatitis...
90 mg 1 times / 2 days multiple, oral Studied dose	unhealthy, ADULT	DLT: Erythematous rash, Stomatitis...

Showing 1 to 5 of 5 entries

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AEs

Show entries

AE	Significance	Dose	Population
Skin rash	grade 3, 100% DLT	300 mg 1 times / week multiple, oral Highest studied dose	unhealthy, ADULT
Skin rash	grade 3, 17.6% DLT	200 mg 1 times / week multiple, oral MTD	unhealthy, ADULT
Dermatitis acneiform	grade 3, 5.9% DLT	200 mg 1 times / week multiple, oral MTD	unhealthy, ADULT
Erythematous rash	grade 3, 5% DLT	60 mg 1 times / 2 days multiple, oral MTD	unhealthy, ADULT
Skin rash	grade 3, 18.4% DLT, Disc. AE	60 mg 1 times / 2 days multiple, oral MTD	unhealthy, ADULT

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252	inhibitor 2,438	inhibitor 2,507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP1 116 CYP19A1 429 BCRP 910 P-gp 1,741	CYP3A 220	CYP3A 142

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP2C9 2,497	inhibitor 4,027	moderate [IC50 >35 uM]
CYP2D6 2,546	inhibitor 4,027	moderate [IC50 >35 uM]
CYP3A4 2,633	inhibitor 4,027	moderate [IC50 >35 uM]
MRP1 232	inhibitor 4,027	moderate [Inhibition 10 uM]
BCRP 985	inhibitor 4,027	moderate

Showing 1 to 5 of 8 entries

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A 220	substrate 4,014	major

Showing 1 to 1 of 1 entries

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PubMed

Show entries

Title	Date	PubMed
The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway.	2011 Apr	21289267
Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels.	2012 Aug	22885370
Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line.	2015 Dec 25	26518876
The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells.	2015 Jan	25164962
Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.	2015 Jan 5	25569083

Showing 1 to 5 of 7 entries

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Patents

Sample Use Guides

In Vivo Use Guide

90 mg weekly (1st 28 days cycle); 135 mg weekly (2nd 28 days cycle)

Route of Administration: Oral

In Vitro Use Guide

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).

Show entries

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-

Preferred 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

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Show entries

Code System

Code

Type

Description

PUBCHEM

24964624

PRIMARY

FDA UNII

51HZG6MP1K

PRIMARY

CAS

1032349-93-1

PRIMARY

WIKIPEDIA

MK-2206

PRIMARY

NCI_THESAURUS

C90581

PRIMARY

Showing 1 to 5 of 5 entries

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ACTIVE MOIETY


					51HZG6MP1K

MK-2206 FREE BASE

SALT/SOLVATE (PARENT)


					4HA45S22ZZ

MK-2206

SALT/SOLVATE (PARENT)


					Q34I3E28IO

MK-2206 DIHYDROCHLORIDE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

C_max

T_1/2

Drug as perpetrator