Details of the Drug

General Information of Drug (ID: DMLDBQ5)

Drug Name
SEN-196
Synonyms EX-527; SEN-0014196; SIRT1 inhibitors (Huntingtons disease), Elixir/Siena; Sirtuin-1 inhibitors (oral, Huntington's disease), Elixir/Siena
Indication
Disease Entry ICD 11 Status REF
Huntington disease 8A01.10 Phase 2 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 248.71
Topological Polar Surface Area (xlogp) 2.5
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 1
Chemical Identifiers
Formula
C13H13ClN2O
IUPAC Name
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
Canonical SMILES
C1CC(C2=C(C1)C3=C(N2)C=CC(=C3)Cl)C(=O)N
InChI
InChI=1S/C13H13ClN2O/c14-7-4-5-11-10(6-7)8-2-1-3-9(13(15)17)12(8)16-11/h4-6,9,16H,1-3H2,(H2,15,17)
InChIKey
FUZYTVDVLBBXDL-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
5113032
ChEBI ID
CHEBI:90369
CAS Number
49843-98-3
TTD ID
D0E3LP

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
NAD-dependent deacetylase sirtuin-1 (SIRT1) TTUF2HO SIR1_HUMAN Inhibitor [3], [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Huntington disease
ICD Disease Classification 8A01.10
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 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: 8100).
2 ClinicalTrials.gov (NCT01521585) A Phase II Safety and Tolerability Study With SEN0014196. U.S. National Institutes of Health.
3 Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69.
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 Pharmacological activation of Sirt1 ameliorates polyglutamine-induced toxicity through the regulation of autophagy.PLoS One.2013 Jun 10;8(6):e64953.
7 SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
8 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.
9 Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J Med Chem. 2009 May 14;52(9):2673-82.
10 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).