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

General Information of Drug (ID: DM0Y8OW)

• Drug Name: N,N-dimethylarginine Drug Info
• Synonyms: N,N-dimethylarginine; ADMA; Asymmetric dimethylarginine; 30315-93-6; Dimethyl-L-arginine; NG,NG-dimethyl-L-arginine; N(G)-Dimethylarginine; Guanidino-N,N-dimethylarginine; N(G),N(G)-Dimethylarginine; (S)-2-Amino-5-(3,3-dimethylguanidino)pentanoic acid; N(G1),N(G1)-Dimethylarginine; Lopac-D-4268; N(5)-((Dimethylamino)iminomethyl)-L-ornithine; N(omega),N(omega)-dimethyl-L-arginine; NG,NG-DIMETHYLARGININE HYDROCHLORIDE; CHEBI:17929; YDGMGEXADBMOMJ-LURJTMIESA-N; N5-[(Dimethylamino)iminomethyl]-L-ornithine

Indication

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

• Cross-matching ID:
  PubChem CID: 123831
  ChEBI ID: CHEBI:17929
  CAS Number: CAS 30315-93-6
  TTD Drug ID: DM0Y8OW

Molecule-Related Drug Atlas

Drug(s) Targeting Nitric-oxide synthase inducible (NOS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[4]
SD-6010	DM9DEYL	Osteoarthritis	FA00-FA05	Phase 3	[5]
MPL-S	DMNDCFY	Endotoxic shock	1G41	Phase 3	[6]
Pimagedine HCl	DMPWH30	Diabetic kidney disease	GB61.Z	Phase 2/3	[7]
GW274150	DMZMCB1	Asthma	CA23	Phase 2	[8]
BXT-51072	DMD8GNB	Cardiovascular disease	BA00-BE2Z	Phase 2	[9]
HP-228	DMNZ35F	Postoperative pain	MG30-MG3Z	Phase 2	[10]
CR-3294	DMHJEZS	Diarrhea	ME05.1	Phase 2	[11]
KD-7040	DME1WV2	Pain	MG30-MG3Z	Phase 2	[12]
LT-1951	DM5N04G	Coronary artery disease	BA80	Phase 1/2	[13]

Drug(s) Targeting Nitric-oxide synthase endothelial (NOS3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tilarginine acetate	DMZBGI8	Myocardial infarction	BA41-BA43	Phase 3	[14]
L-NAME	DM01SR6	Hypertension	BA00-BA04	Phase 2	[15]
ACCLAIM	DM0FGDO	Angina pectoris	BA40	Phase 2	[16]
VAS-203	DMKU93J	Brain injury	NA07.Z	Phase 2	[17]
MTR105	DMT0K4F	Hypotension	BA20-BA21	Phase 2	[18]
Autologous cell based gene therapy	DMQA1VT	Pulmonary hypertension	BB01	Phase 1	[19]
L-NIL	DM6Y49D	N. A.	N. A.	Terminated	[20]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[21]
2-Methyl-2,4-Pentanediol	DMD45CU	Discovery agent	N.A.	Investigative	[21]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[22]

Drug(s) Affected By Solute carrier organic anion transporter family member 4C1 (SLCO4C1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[23]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[24]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[25]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[26]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[27]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[28]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]
Demecolcine	DMCZQGK	Solid tumour/cancer	2A00-2F9Z	Approved	[30]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[31]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Nitric-oxide synthase endothelial (NOS3)	TTCM4B3	NOS3_HUMAN	Inhibitor	[2]
Nitric-oxide synthase inducible (NOS2)	TTF10I9	NOS2_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Solute carrier organic anion transporter family member 4C1 (SLCO4C1)	OTVILUUN	SO4C1_HUMAN	Regulation of Drug Effects	[3]

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: 5229).
• [2] Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease. Clin Chem Lab Med. 2007;45(12):1683-7.
• [3] The renal transport protein OATP4C1 mediates uptake of the uremic toxin asymmetric dimethylarginine (ADMA) and efflux of cardioprotective L-homoarginine. PLoS One. 2019 Mar 13;14(3):e0213747. doi: 10.1371/journal.pone.0213747. eCollection 2019.
• [4] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [5] A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Ann Rheum Dis. 2013 Feb;72(2):187-95.
• [6] Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages. Infect Immun. 1997 Aug;65(8):3239-47.
• [7] Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia. Brain Res. 2008 Sep 16;1230:138-49.
• [8] GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int. 2003 Mar;63(3):853-65.
• [9] Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress. Am J Physiol Cell Physiol. 2000 Dec;279(6):C1880-8.
• [10] HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro. J Pharmacol Exp Ther. 1995 Nov;275(2):584-91.
• [11] Efficacy of CR3294, a new benzamidine derivative, in the prevention of 5-fluorouracil-induced gastrointestinal mucositis and diarrhea in mice. Cancer Chemother Pharmacol. 2010 October; 66(5): 819-827.
• [12] WO patent application no. 2014,0214,08, Method for treating cancer by anticancer agent co-administration.
• [13] Critical role of L-arginine in endothelial cell survival during oxidative stress. Circulation. 2003 May 27;107(20):2607-14.
• [14] Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial. JAMA. 2007 Apr 18;297(15):1657-66.
• [15] Counter-regulation by atorvastatin of gene modulations induced by L-NAME hypertension is associated with vascular protection. Vascul Pharmacol. 2009 Oct;51(4):253-61.
• [16] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [17] Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA). J Neurotrauma. 2014 Oct 1;31(19):1599-606.
• [18] Nitric oxide synthase inhibitor (MTR-105) during open-heart surgery. A pilot double-blind placebo-controlled study of hemodynamic effects and safety. Cardiology. 2008;111(3):181-7.
• [19] Feasibility of using autologous transplantation to evaluate hematopoietic stem cell-based gene therapy strategies in transgenic mouse models of human disease. Mol Ther. 2002 Sep;6(3):422-8.
• [20] Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43.
• [21] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [22] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [23] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [24] 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.
• [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] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [27] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [28] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [29] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [30] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [31] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [32] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.