MK-2206   Click here for help

GtoPdb Ligand ID: 7945

Synonyms: MK 2206
Compound class: Synthetic organic
Comment: MK-2206 is an orally bioavailable allosteric inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity [2-4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 89.07
Molecular weight 407.17
XLogP 5.13
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=c1[nH]nc2n1ccc1c2cc(c(n1)c1ccc(cc1)C1(N)CCC1)c1ccccc1
Isomeric SMILES O=c1[nH]nc2n1ccc1c2cc(c(n1)c1ccc(cc1)C1(N)CCC1)c1ccccc1
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)
InChI Key ULDXWLCXEDXJGE-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, Ueno Y, Hatch H, Majumder PK, Pan BS et al.. (2010)
MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo.
Mol Cancer Ther, 9 (7): 1956-67. [PMID:20571069]
2. Holland WS, Chinn DC, Lara Jr PN, Gandara DR, Mack PC. (2015)
Effects of AKT inhibition on HGF-mediated erlotinib resistance in non-small cell lung cancer cell lines.
J Cancer Res Clin Oncol, 141 (4): 615-26. [PMID:25323938]
3. Lin YH, Chen BY, Lai WT, Wu SF, Guh JH, Cheng AL, Hsu LC. (2015)
The Akt inhibitor MK-2206 enhances the cytotoxicity of paclitaxel (Taxol) and cisplatin in ovarian cancer cells.
Naunyn Schmiedebergs Arch Pharmacol, 388 (1): 19-31. [PMID:25164962]
4. Liu R, Liu D, Trink E, Bojdani E, Ning G, Xing M. (2011)
The Akt-specific inhibitor MK2206 selectively inhibits thyroid cancer cells harboring mutations that can activate the PI3K/Akt pathway.
J Clin Endocrinol Metab, 96 (4): E577-85. [PMID:21289267]
5. Yan L. 
Abstract #DDT01-1: MK-2206: A potent oral allosteric AKT inhibitor.
Accessed on 18/11/2014. Modified on 18/11/2014. AACR Meeting Abstracts Online; http://aacrmeetingabstracts.org, http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2009/2_Annual_Meeting/DDT01-1?maxtoshow=&hits=10&RESULTFORMAT=1&title=MK-2206&andorexacttitle=and&andorexacttitleabs=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&fdate=1/1/2008&tdate=12/31/2010&resourcetype=HWCIT
6. Yan L. (2009)
MK-2206: a potent oral allosteric AKT inhibitor.[Abstract].
AACR Annual Meeting 2009,: Abstract Number: DDT01-1.