Details of the Drug

General Information of Drug (ID: DM8H7OA)

Drug Name
Netoglitazone
Synonyms
Isaglitazone; Netoglitazone [USAN]; MCC 555; MCC-555; RWJ-241947; Netoglitazone (USAN/INN); 5-((6-((2-fluorophenyl)methoxy)-2-naphthalenyl)methyl)-2,4-thiazolidinedione; 5-({6-[(2-fluorobenzyl)oxy]naphthalen-2-yl}methyl)-1,3-thiazolidine-2,4-dione; 5-[[6-[(2-fluorophenyl)methoxy]naphthalen-2-yl]methyl]-1,3-thiazolidine-2,4-dione
Indication
Disease Entry ICD 11 Status REF
Non-alcoholic fatty liver disease DB92 Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 381.4
Logarithm of the Partition Coefficient (xlogp) 4.9
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C21H16FNO3S
IUPAC Name
5-[[6-[(2-fluorophenyl)methoxy]naphthalen-2-yl]methyl]-1,3-thiazolidine-2,4-dione
Canonical SMILES
C1=CC=C(C(=C1)COC2=CC3=C(C=C2)C=C(C=C3)CC4C(=O)NC(=O)S4)F
InChI
InChI=1S/C21H16FNO3S/c22-18-4-2-1-3-16(18)12-26-17-8-7-14-9-13(5-6-15(14)11-17)10-19-20(24)23-21(25)27-19/h1-9,11,19H,10,12H2,(H,23,24,25)
InChIKey
PKWDZWYVIHVNKS-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
204109
CAS Number
161600-01-7
DrugBank ID
DB09199
TTD ID
D02TGD
INTEDE ID
DR1140

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) TTZMAO3 PPARG_HUMAN Modulator [2]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Cadherin-1 (CDH1) OTFJMXPM CADH1_HUMAN Gene/Protein Processing [4]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [4]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Gene/Protein Processing [5]
G1/S-specific cyclin-E1 (CCNE1) OTLD7UID CCNE1_HUMAN Gene/Protein Processing [4]
Growth/differentiation factor 15 (GDF15) OTWQN50N GDF15_HUMAN Gene/Protein Processing [5]
Krueppel-like factor 4 (KLF4) OT4O9RQW KLF4_HUMAN Gene/Protein Processing [5]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Gene/Protein Processing [6]
Platelet glycoprotein 4 (CD36) OT5CZWKY CD36_HUMAN Gene/Protein Processing [4]
Prostate-specific antigen (KLK3) OTFGSBFJ KLK3_HUMAN Gene/Protein Processing [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-alcoholic fatty liver disease
ICD Disease Classification DB92
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) DTT PPARG 2.41E-01 -0.06 -0.25
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.04E-02 6.29E-02 3.54E-01
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: 2707).
2 Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat. Bone. 2006 Jan;38(1):74-84.
3 Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005 May;77(5):404-14.
4 RWJ-241947 (MCC-555), a unique peroxisome proliferator-activated receptor-gamma ligand with antitumor activity against human prostate cancer in vitro and in beige/nude/ X-linked immunodeficient mice and enhancement of apoptosis in myeloma cells induced by arsenic trioxide. Clin Cancer Res. 2004 Feb 15;10(4):1508-20. doi: 10.1158/1078-0432.ccr-0476-03.
5 A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4. Toxicol Appl Pharmacol. 2012 Sep 1;263(2):225-32. doi: 10.1016/j.taap.2012.06.014. Epub 2012 Jun 30.
6 Stable reporter cell lines for peroxisome proliferator-activated receptor (PPAR)-mediated modulation of gene expression. Anal Biochem. 2011 Jul 1;414(1):77-83. doi: 10.1016/j.ab.2011.02.032. Epub 2011 Feb 24.