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]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 248.71
Logarithm of the Partition Coefficient (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 [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
ATP-binding cassette sub-family C member 3 (ABCC3) OTC3IJV4 MRP3_HUMAN Gene/Protein Processing [3]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Gene/Protein Processing [3]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Post-Translational Modifications [4]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Gene/Protein Processing [5]
NAD-dependent protein deacetylase sirtuin-2 (SIRT2) OT5Q6SVK SIR2_HUMAN Gene/Protein Processing [6]
NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SIRT3) OTMEF544 SIR3_HUMAN Gene/Protein Processing [7]
NAD-dependent protein deacylase sirtuin-6 (SIRT6) OTF755ZO SIR6_HUMAN Gene/Protein Processing [7]
Nitric oxide synthase 3 (NOS3) OTLDT7NR NOS3_HUMAN Post-Translational Modifications [8]
RE1-silencing transcription factor (REST) OTLL92LQ REST_HUMAN Gene/Protein Processing [9]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Protein Interaction/Cellular Processes [10]
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 Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69.
3 Inhibition of sirtuins 1 and 2 impairs cell survival and migration and modulates the expression of P-glycoprotein and MRP3 in hepatocellular carcinoma cell lines. Toxicol Lett. 2018 Jun 1;289:63-74. doi: 10.1016/j.toxlet.2018.03.011. Epub 2018 Mar 12.
4 SIRT1 inhibition restores apoptotic sensitivity in p53-mutated human keratinocytes. Toxicol Appl Pharmacol. 2014 Jun 15;277(3):288-97. doi: 10.1016/j.taap.2014.04.001. Epub 2014 Apr 12.
5 SIRT1 modulates expression of matrix metalloproteinases in human dermal fibroblasts. Br J Dermatol. 2010 Oct;163(4):689-94. doi: 10.1111/j.1365-2133.2010.09825.x.
6 Non-specific SIRT inhibition as a mechanism for the cytotoxicity of ginkgolic acids and urushiols. Toxicol Lett. 2014 Sep 2;229(2):374-80. doi: 10.1016/j.toxlet.2014.07.002. Epub 2014 Jul 3.
7 Sirtuins are Unaffected by PARP Inhibitors Containing Planar Nicotinamide Bioisosteres. Chem Biol Drug Des. 2016 Mar;87(3):478-82. doi: 10.1111/cbdd.12680. Epub 2015 Nov 26.
8 Salvianolic acid inhibits the effects of high glucose on vascular endothelial dysfunction by modulating the Sirt1-eNOS pathway. J Biochem Mol Toxicol. 2019 Feb;33(2):e22245. doi: 10.1002/jbt.22245. Epub 2018 Nov 15.
9 Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death. Toxicol Appl Pharmacol. 2015 Nov 1;288(3):387-98. doi: 10.1016/j.taap.2015.08.010. Epub 2015 Aug 22.
10 Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway. Mol Nutr Food Res. 2015 Aug;59(8):1443-57. doi: 10.1002/mnfr.201500016. Epub 2015 May 28.