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

General Information of Drug (ID: DMUGQIV)

• Drug Name: 2-chloro-5-nitro-N-phenylbenzamide Drug Info
• Synonyms: 2-Chloro-5-nitro-N-phenylbenzamide; GW9662; 22978-25-2; GW 9662; 2-Chloro-5-nitrobenzanilide; GW-9662; MLS001056751; CHEBI:79993; 2-Chloro-5-nitro-N-phenyl-benzamide; 2-Chloro-5-nitro-N-4-phenylbenzamide; benzamide, 2-chloro-5-nitro-N-phenyl-; SMR000326735; (2-chloro-5-nitrophenyl)-N-benzamide; SR-01000075999; Tocris-1508; Spectrum5_001989; Lopac-M-6191; AC1LD8S0; DSSTox_RID_79570; DSSTox_CID_20723; DSSTox_GSID_40723; Lopac0_000798; KBioGR_000361; KBioSS_000361; BSPBio_001021; SCHEMBL420231; CHEMBL375270; GTPL3442; cid_644213

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1] , [2]

• Cross-matching ID:
  PubChem CID: 644213
  ChEBI ID: CHEBI:79993
  CAS Number: CAS 22978-25-2
  TTD Drug ID: DMUGQIV
  INTEDE Drug ID: DR2165

Molecule-Related Drug Atlas

Drug(s) Metabolized By Oxygen-insensitive NADPH nitroreductase B (nfsB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AI3-23606	DMHMT49	Trypanosomiasis	1D51-1F53	Phase 1	[5]
Nitroimidazole	DMMY2S5	Trypanosomiasis	1D51-1F53	Investigative	[5]
CL-205086	DMB6XUY	Intestinal amebiasis	1A36	Investigative	[5]

Drug(s) Metabolized By Oxygen-insensitive NADPH nitroreductase A (nfsA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ornidazole	DM6QHDJ	Amoebiasis	1A36	Approved	[6]
Nitrazepam	DMEGIQ6	Epilepsy	8A60-8A68	Approved	[6]
AI3-23606	DMHMT49	Trypanosomiasis	1D51-1F53	Phase 1	[5]
Nitroimidazole	DMMY2S5	Trypanosomiasis	1D51-1F53	Investigative	[5]
CL-205086	DMB6XUY	Intestinal amebiasis	1A36	Investigative	[5]

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	[7]
AD-5075	DM1SLJ9	Type-2 diabetes	5A11	Terminated	[8]
L-783483	DM6OTGE	Discovery agent	N.A.	Investigative	[9]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[10]
L-796449	DMWTGQM	Discovery agent	N.A.	Investigative	[11]
L-165461	DMKBSGN	Discovery agent	N.A.	Investigative	[11]
AD-5061	DM5WV13	Discovery agent	N.A.	Investigative	[12]
TZD18	DMVCHOX	Discovery agent	N.A.	Investigative	[13]
(9Z,12E)-12-nitrooctadeca-9,12-dienoic acid	DM2REIN	Discovery agent	N.A.	Investigative	[14]
reglitazar	DMQ3ER0	Discovery agent	N.A.	Investigative	[15]

Drug(s) Targeting Retinoic acid receptor RXR-alpha (RXRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alitretinoin	DMME8LH	Kaposi sarcoma	2B57	Approved	[16]
Bexarotene	DMOBIKY	Cutaneous T-cell lymphoma	2B01	Approved	[17]
AGN-34	DM5ECDM	Discovery agent	N.A.	Investigative	[18]
LG100754	DMEK4FY	Discovery agent	N.A.	Investigative	[19]
(5BETA)-PREGNANE-3,20-DIONE	DMVQ6RN	Discovery agent	N.A.	Investigative	[1]
Phytanic acid	DMSZ1RB	Discovery agent	N.A.	Investigative	[20]
CD3254	DM38MU1	Discovery agent	N.A.	Investigative	[21]
UVI3003	DM95UI1	Discovery agent	N.A.	Investigative	[22]
Tributylstannanyl	DMHN7CB	Discovery agent	N.A.	Investigative	[1]
methoprene acid	DM58A0W	Discovery agent	N.A.	Investigative	[23]

Drug(s) Targeting Peroxisome proliferator-activated receptor gamma (PPAR-gamma)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[24]
Pioglitazone	DMKJ485	Diabetic complication	5A2Y	Approved	[25]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[26]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[27]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[25]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[28]
Muraglitazar	DMG3NFZ	N. A.	N. A.	Phase 3	[29]
Rosiglitazone + metformin	DMPIDXT	Diabetic complication	5A2Y	Phase 3	[27]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[30]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[31]

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	Inhibitor	[1]
PPAR-gamma messenger RNA (PPARG mRNA)	TTT2SVW	PPARG_HUMAN	Inhibitor	[3]
Retinoic acid receptor RXR-alpha (RXRA)	TT6PEUO	RXRA_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Oxygen-insensitive NADPH nitroreductase A (nfsA)	DEX5D46	NFSA_SALTY	Substrate	[4]
Oxygen-insensitive NADPH nitroreductase B (nfsB)	DEOWDK1	NFSB_SALTY	Substrate	[4]

References

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• [2] 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: 3442).
• [3] 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.
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• [5] Delamanid is not metabolized by Salmonella or human nitroreductases: a possible mechanism for the lack of mutagenicity. Regul Toxicol Pharmacol. 2017 Mar;84:1-8.
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• [7] 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.
• [8] 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.
• [9] Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25.
• [10] 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.
• [11] Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.
• [12] A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26.
• [13] A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8.
• [14] 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.
• [15] Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol. 1999 Jan 8;364(2-3):211-9.
• [16] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):30-4.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [18] Farnesoid X receptor: from structure to potential clinical applications. J Med Chem. 2005 Aug 25;48(17):5383-403.
• [19] The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo. Mol Endocrinol. 2001 Aug;15(8):1360-9.
• [20] Phytanic acid is a retinoid X receptor ligand. Eur J Biochem. 1996 Feb 15;236(1):328-33.
• [21] Co-regulator recruitment and the mechanism of retinoic acid receptor synergy. Nature. 2002 Jan 10;415(6868):187-92.
• [22] Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators thro... J Biol Chem. 2005 Jan 14;280(2):1625-33.
• [23] Activation of mammalian retinoid X receptors by the insect growth regulator methoprene. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6157-60.
• [24] Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int J Cancer. 2003 May 1;104(5):597-602.
• [25] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [26] Tolerability and pharmacokinetics of lobeglitazone, a novel peroxisome proliferator-activated receptor-gamma agonist, after a single oral administration in healthy female subjects. Clin Drug Investig. 2014 Jul;34(7):467-74.
• [27] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [28] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [29] Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with... Clin Ther. 2005 Aug;27(8):1181-95.
• [30] A randomized-controlled trial to investigate the effects of rivoglitazone, a novel PPAR gamma agonist on glucose-lipid control in type 2 diabetes. Diabetes Obes Metab. 2011 Sep;13(9):806-13.
• [31] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.