Details of the Drug

General Information of Drug (ID: DMMIR1K)

Drug Name
GSK184072
Synonyms
Flutimide; 162666-34-4; AC1O5YLM; AKOS027326745; (5Z)-1-hydroxy-3-isobutyl-5-(2-methylpropylidene)pyrazine-2,6-dione; 2,6-(1H,3H)-Pyrazinedione, 1-hydroxy-5-(2-methylpropyl)-3-(2-methylpropylidene)-, (Z)-; 2,6-(1H,3H)-Pyrazinedione, 1-hydroxy-5-(2-methylpropyl)-3-(2-methylpropylidene)-, (3Z)-; (5Z)-1-hydroxy-3-(2-methylpropyl)-5-(2-methylpropylidene)pyrazine-2,6-dione
Indication
Disease Entry ICD 11 Status REF
Colon cancer 2B90.Z Discontinued in Phase 2 [1]
Hematologic tumour 2B33.Y Discontinued in Phase 2 [1]
Type-2 diabetes 5A11 Discontinued in Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 238.28
Topological Polar Surface Area (xlogp) 1.7
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 4
Chemical Identifiers
Formula
C12H18N2O3
IUPAC Name
(5Z)-1-hydroxy-3-(2-methylpropyl)-5-(2-methylpropylidene)pyrazine-2,6-dione
Canonical SMILES
CC(C)CC1=N/C(=C\\C(C)C)/C(=O)N(C1=O)O
InChI
InChI=1S/C12H18N2O3/c1-7(2)5-9-11(15)14(17)12(16)10(13-9)6-8(3)4/h5,7-8,17H,6H2,1-4H3/b9-5-
InChIKey
SIXHCCPAJIVTOY-UITAMQMPSA-N
Cross-matching ID
PubChem CID
6443207
CAS Number
162666-34-4
TTD ID
D0R3EL

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
CAP-dependent endonuclease (CDE) TTTG60L NOUNIPROTAC Inhibitor [2]
NAD-dependent deacetylase sirtuin-1 (SIRT1) TTUF2HO SIR1_HUMAN Activator [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Colon cancer
ICD Disease Classification 2B90.Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
NAD-dependent deacetylase sirtuin-1 (SIRT1) DTT SIRT1 7.82E-01 -0.16 -0.27
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024569)
2 Synthesis of natural flutimide and analogous fully substituted pyrazine-2,6-diones, endonuclease inhibitors of influenza virus. J Org Chem. 2001 Aug 10;66(16):5504-16.
3 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
4 Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
5 Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.
6 Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69.
7 Pharmacological activation of Sirt1 ameliorates polyglutamine-induced toxicity through the regulation of autophagy.PLoS One.2013 Jun 10;8(6):e64953.
8 SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
9 The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells. PLoS One. 2015 Jul 30;10(7):e0134391.
10 Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J Med Chem. 2009 May 14;52(9):2673-82.
11 Anti-influenza virus activities of 4-substituted 2,4-dioxobutanoic acid inhibitors. Antimicrob Agents Chemother. 1996 May;40(5):1304-7.