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
UNII
QOV2JZ647A
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.