Details of the Drug

General Information of Drug (ID: DMT1OZ6)

Drug Name
MK-2206
Synonyms
MK-2206; 1032349-93-1; UNII-51HZG6MP1K; MK 2206; 51HZG6MP1K; CHEMBL1079175; CHEBI:67271; NCGC00186465-01; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one; DSSTox_RID_83143; DSSTox_CID_28874; 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-1,2,4-Triazolo[3,4-f][1,6]naphthyridin-3(2H)-one; 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-;
Indication
Disease Entry ICD 11 Status REF
Rectal adenocarcinoma 2B92 Phase 2 [1], [2]
Nasopharyngeal carcinoma 2B6B Investigative [3]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 407.5
Topological Polar Surface Area (xlogp) 3
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 4
Chemical Identifiers
Formula
C25H21N5O
IUPAC Name
8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-2H-[1,2,4]triazolo[3,4-f][1,6]naphthyridin-3-one
Canonical SMILES
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
Cross-matching ID
PubChem CID
24964624
ChEBI ID
CHEBI:67271
CAS Number
1032349-93-1
TTD ID
D0W3RW

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
E2 ubiquitin-conjugating enzyme T (UBE2T) TT0A1R8 UBE2T_HUMAN Inhibitor [3]
RAC-gamma serine/threonine-protein kinase (AKT3) TTAZ05C AKT3_HUMAN Modulator [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Rectal adenocarcinoma
ICD Disease Classification 2B92
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
RAC-gamma serine/threonine-protein kinase (AKT3) DTT AKT3 6.79E-01 -0.02 -0.08
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7945).
2 ClinicalTrials.gov (NCT01249105) MK-2206 for Recurrent Malignant Glioma. U.S. National Institutes of Health.
3 UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3/-catenin pathway.Oncotarget. 2016 Mar 22;7(12):15161-72.
4 First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors.J Clin Oncol.2011 Dec 10;29(35):4688-95.
5 The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood. 2014 Oct 2;124(14):2190-5.
6 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
7 Inhibiting the akt pathway in cancer treatment: three leading candidates. P T. 2011 Apr;36(4):225-7.
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 DOI: 10.1016/S1359-6349(10)71767-5
10 A first-in-human phase I trial of LY2780301, a dual p70 S6 kinase and Akt Inhibitor, in patients with advanced or metastatic cancer. Invest New Drugs. 2015 Jun;33(3):710-9.
11 Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer
12 Phase 0 clinical chemoprevention trial of the Akt inhibitor SR13668. Cancer Prev Res (Phila). 2011 Mar;4(3):347-53.
13 Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT.Invest New Drugs.2011 Dec;29(6):1381-9.
14 Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.Cancer Res.2008 Apr 1;68(7):2366-74.