Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMTHB2Y)

• Drug Name: nTzDpa Drug Info
• Synonyms: nTzDpa; 118414-59-8; 5-Chloro-1-(4-Chlorobenzyl)-3-(Phenylthio)-1h-Indole-2-Carboxylic Acid; 5-CHLORO-1-[(4-CHLOROPHENYL)METHYL]-3-(PHENYLTHIO)-1H-INDOLE-2-CARBOXYLIC ACID; CHEMBL370152; 1H-Indole-2-carboxylicacid, 5-chloro-1-[(4-chlorophenyl)methyl]-3-(phenylthio)-; NZA; ACMC-1CBOZ; SCHEMBL6709652; GTPL2699; CTK0H3131; DTXSID40433292; MolPort-003-983-790; HMS3268N03; ZINC1492396; BDBM50173365; BS0133; AKOS024456957; NCGC00092313-01; RT-014770; KB-245430; B6955; J-003750; BRD-K54708045-001-01-3

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 9954280
  CAS Number: CAS 118414-59-8
  TTD Drug ID: DMTHB2Y

Molecule-Related Drug Atlas

Drug(s) Targeting PPAR-gamma messenger RNA (PPARG mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bardoxolone methyl	DMODA2X	Mixed connective tissue disease	4A43.3	Phase 3	[4]
AD-5075	DM1SLJ9	Type-2 diabetes	5A11	Terminated	[5]
2-chloro-5-nitro-N-phenylbenzamide	DMUGQIV	Discovery agent	N.A.	Investigative	[6]
L-783483	DM6OTGE	Discovery agent	N.A.	Investigative	[7]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[8]
L-796449	DMWTGQM	Discovery agent	N.A.	Investigative	[9]
L-165461	DMKBSGN	Discovery agent	N.A.	Investigative	[9]
AD-5061	DM5WV13	Discovery agent	N.A.	Investigative	[10]
TZD18	DMVCHOX	Discovery agent	N.A.	Investigative	[11]
(9Z,12E)-12-nitrooctadeca-9,12-dienoic acid	DM2REIN	Discovery agent	N.A.	Investigative	[12]

Drug(s) Affected By Peroxisome proliferator-activated receptor gamma (PPARG)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[14]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[16]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[18]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[21]
Stavudine	DM6DEK9	Human immunodeficiency virus infection	1C62	Approved	[22]

Drug(s) Affected By Fatty acid 2-hydroxylase (FA2H)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[24]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[25]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[3]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[28]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[29]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[30]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PPAR-gamma messenger RNA (PPARG mRNA)	TTT2SVW	PPARG_HUMAN	Agonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Fatty acid 2-hydroxylase (FA2H)	OT8HA13U	FA2H_HUMAN	Gene/Protein Processing	[3]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Protein Interaction/Cellular Processes	[2]

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: 2699).
• [2] Distinct properties and advantages of a novel peroxisome proliferator-activated protein [gamma] selective modulator. Mol Endocrinol. 2003 Apr;17(4):662-76.
• [3] Induction of the fatty acid 2-hydroxylase (FA2H) gene by (9)-tetrahydrocannabinol in human breast cancer cells. J Toxicol Sci. 2013;38(2):305-8. doi: 10.2131/jts.38.305.
• [4] A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma. Mol Endocrinol. 2000 Oct;14(10):1550-6.
• [5] Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology. 1996 Oct;137(10):4189-95.
• [6] Tryptophan-containing dipeptide derivatives as potent PPARgamma antagonists: design, synthesis, biological evaluation, and molecular modeling. Eur J Med Chem. 2008 Dec;43(12):2699-716.
• [7] Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25.
• [8] The antidiabetic agent LG100754 sensitizes cells to low concentrations of peroxisome proliferator-activated receptor gamma ligands. J Biol Chem. 2002 Apr 12;277(15):12503-6.
• [9] Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.
• [10] A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26.
• [11] A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8.
• [12] Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by nitroalkene fatty acids: importance of nitration position and degree ... J Med Chem. 2009 Aug 13;52(15):4631-9.
• [13] COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
• [14] Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines. Toxicol Appl Pharmacol. 2014 Nov 1;280(3):550-60.
• [15] The effect of quercetin and kaempferol aglycones and glucuronides on peroxisome proliferator-activated receptor-gamma (PPAR-). Food Funct. 2015 Apr;6(4):1098-107. doi: 10.1039/c5fo00076a.
• [16] Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3951-6. doi: 10.1073/pnas.96.7.3951.
• [17] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [18] Glucosamine sulfate reduces prostaglandin E(2) production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1. J Rheumatol. 2012 Mar;39(3):635-44. doi: 10.3899/jrheum.110621. Epub 2011 Nov 15.
• [19] Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes. Toxicol Appl Pharmacol. 2013 Dec 15;273(3):435-41. doi: 10.1016/j.taap.2013.10.005. Epub 2013 Oct 12.
• [20] Regulatory role of KEAP1 and NRF2 in PPAR expression and chemoresistance in human non-small-cell lung carcinoma cells. Free Radic Biol Med. 2012 Aug 15;53(4):758-68. doi: 10.1016/j.freeradbiomed.2012.05.041. Epub 2012 Jun 7.
• [21] Aspirin inhibits MMP-9 mRNA expression and release via the PPARalpha/gamma and COX-2/mPGES-1-mediated pathways in macrophages derived from THP-1 cells. Biomed Pharmacother. 2010 Feb;64(2):118-23. doi: 10.1016/j.biopha.2009.04.033. Epub 2009 Oct 17.
• [22] Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients. Antivir Ther. 2003 Aug;8(4):323-31.
• [23] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [24] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [25] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [26] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [27] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [28] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [29] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [30] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [31] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.