Details of the Drug

General Information of Drug (ID: DM9LRKB)

• Drug Name: Nicotinamide-Adenine-Dinucleotide
• Synonyms: NICOTINAMIDE-ADENINE-DINUCLEOTIDE (ACIDIC FORM); AC1NRCGS; [[(2R,3S,4R,5R)-5-(6-amino-7H-purin-9-ium-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 663.4
  Topological Polar Surface Area (xlogp); -6
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 7
  Hydrogen Bond Acceptor Count (hbondacc); 18
• Chemical Identifiers:
  Formula: C21H27N7O14P2
  IUPAC Name: [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate
  Canonical SMILES: C1=CC(=C[N+](=C1)[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)([O-])OP(=O)(O)OC[C@@H]3[C@H]([C@H]([C@@H](O3)N4C=NC5=C(N=CN=C54)N)O)O)O)O)C(=O)N
  InChI: InChI=1S/C21H27N7O14P2/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(32)14(30)11(41-21)6-39-44(36,37)42-43(34,35)38-5-10-13(29)15(31)20(40-10)27-3-1-2-9(4-27)18(23)33/h1-4,7-8,10-11,13-16,20-21,29-32H,5-6H2,(H5-,22,23,24,25,33,34,35,36,37)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1
  InChIKey: BAWFJGJZGIEFAR-NNYOXOHSSA-N
• Cross-matching ID:
  PubChem CID: 5892
  ChEBI ID: CHEBI:44215
  CAS Number: 53-84-9
  TTD ID: D0R6JE

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adenosylhomocysteinase (AHCY)	TTE2KUJ	SAHH_HUMAN	Inhibitor	[1]
Alpha-glucosidase (GLA)	TTHCF4J	LYAG_HUMAN; GANAB_HUMAN; GANC_HUMAN	Inhibitor	[1]
Bacterial Dehydroquinate synthase (Bact aroB)	TTPS7KA	AROB_ECOLI	Inhibitor	[1]
Bacterial Fatty acid synthetase I (Bact inhA)	TTVTX4N	INHA_MYCTU	Inhibitor	[1]
Bacterial Flavohemoglobin (Bact hmp)	TTNAW8S	HMP_ECOLI	Inhibitor	[1]
Bacterial NH(3)-dependent NAD(+) synthetase (Bact nadE)	TT8WCXO	NADE_ECOLI	Inhibitor	[1]
Bacterial Nicotinate-nucleotide adenylyltransferase (Bact nadD)	TT1NFO3	NADD_ECOLI	Inhibitor	[1]
Biliverdin reductase A (BLVRA)	TTJBPN3	BIEA_HUMAN	Inhibitor	[1]
Deoxyhypusine synthase (DHPS)	TTBO2A9	DHYS_HUMAN	Inhibitor	[1]
Entamoeba Alcohol dehydrogenase 2 (Entamo ADH2)	TTJS7O4	ADH2_ENTHI	Inhibitor	[1]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)	TTIWB6L	DHB1_HUMAN	Inhibitor	[1]
Estradiol 17 beta-dehydrogenase 4 (HSD17B4)	TTL1WGS	DHB4_HUMAN	Inhibitor	[1]
Glutathione reductase (GR)	TTEP6RV	GSHR_HUMAN	Inhibitor	[1]
Haemophilus influenzae NadR protein (Hae-influ nadR)	TTWUDYC	NADR_HAEIN	Inhibitor	[1]
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Inhibitor	[1]
Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2)	TTTB4UP	IMDH2_HUMAN	Inhibitor	[1]
Intestinal maltase-glucoamylase (MGAM)	TTXWASR	MGA_HUMAN	Inhibitor	[1]
L-lactate dehydrogenase (LDH)	TTAZHU0	LDHA_HUMAN; LDHB_HUMAN; LDHC_HUMAN	Inhibitor	[1]
Mitochondrial aldehyde dehydrogenase (ALDH2)	TTFLN4T	ALDH2_HUMAN	Inhibitor	[1]
Plasmodium Enoyl-ACP reductase (Malaria fabI)	TTNX2CS	Q965D5_PLAFA	Inhibitor	[1]
Pseudomonas Nicotinate-nucleotide adenylyltransferase (Pseudo nadD)	TTKVNRF	NADD_PSEAE	Inhibitor	[1]
Sorbitoldehydrogenase (SORD)	TTLSRBZ	DHSO_HUMAN	Inhibitor	[1]
Trypanosoma Dihydrolipoamide dehydrogenase (Trypano LPD)	TTBKQL3	DLDH_TRYCR	Inhibitor	[1]
UDP-glucose 4-epimerase (GALE)	TTGRHIB	GALE_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
HMG-CoA reductase (HMGCR)	DTT	HMGCR	1.01E-05	0.65	1.53

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] Correlation of binding constants and molecular modelling of inhibitors in the active sites of aldose reductase and aldehyde reductase. Bioorg Med Chem. 2009 Feb 1;17(3):1244-50.
• [3] Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) as a target for anti-amoebic agents. J Antimicrob Chemother. 2004 Jul;54(1):56-9.
• [4] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [5] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [6] The purification and properties of glutathione reductase from the cestode Moniezia expansa. Int J Biochem Cell Biol. 1995 Apr;27(4):393-401.
• [7] Thioredoxin reductase inhibitors: a patent review.Expert Opin Ther Pat. 2017 May;27(5):547-556.
• [8] Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate. J Med Chem. 2005 Nov 17;48(23):7400-10.
• [9] In vitro inhibition of human erythrocyte glutathione reductase by some new organic nitrates. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3661-3.
• [10] Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal... Toxicol Appl Pharmacol. 2008 Oct 15;232(2):327-36.
• [11] Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries. J Med Chem. 2008 Jul 24;51(14):4188-99.
• [12] Substituted 6-phenyl-2-naphthols. Potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1): design,... J Med Chem. 2008 Aug 14;51(15):4685-98.
• [13] Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors... J Med Chem. 2008 Apr 10;51(7):2158-69.
• [14] New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxyst... J Med Chem. 2009 Nov 12;52(21):6724-43.
• [15] A novel aldehyde dehydrogenase-3 activator leads to adult salivary stem cell enrichment in vivo. Clin Cancer Res. 2011 Dec 1;17(23):7265-72.
• [16] Clinical pipeline report, company report or official report of Gilead.
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [19] Structure of daidzin, a naturally occurring anti-alcohol-addiction agent, in complex with human mitochondrial aldehyde dehydrogenase. J Med Chem. 2008 Aug 14;51(15):4482-7.
• [20] 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. (Target id: 2595).
• [21] A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis. 2002 Jun;162(2):373-9.
• [22] Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64.
• [23] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [24] Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia. Arzneimittelforschung. 2001;51(3):197-203.
• [25] New dimension of statin action on ApoB atherogenicity. Clin Cardiol. 2003 Jan;26(1 Suppl 1):I7-10.
• [26] Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.
• [27] Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46.
• [28] Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
• [29] Green tea catechins potentiate triclosan binding to enoyl-ACP reductase from Plasmodium falciparum (PfENR). J Med Chem. 2007 Feb 22;50(4):765-75.
• [30] Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem. 2006 Jun 1;49(11):3345-53.
• [31] Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97.
• [32] Sorbitol dehydrogenase: a novel target for adjunctive protection of ischemic myocardium. FASEB J. 2003 Dec;17(15):2331-3.
• [33] Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases. J Med Chem. 1994 Oct 28;37(22):3701-6.
• [34] Absorption, elimination, and metabolism of CS-1036, a novel -amylase inhibitor in rats and monkeys, and the relationship between gastrointestinal distribution and suppression of glucose absorption.Drug Metab Dispos.2013 Apr;41(4):878-87.
• [35] ClinicalTrials.gov (NCT03533673) AAV2/8-LSPhGAA in Late-Onset Pompe Disease. U.S. National Institutes of Health.
• [36] US patent application no. 2012,0251,516, PHARMACEUTICAL COMPOSITION FOR TREATING CANCER COMPRISING TRYPSINOGEN AND/OR CHYMOTRYPSINOGEN AND AN ACTIVE AGENT SELECTED FROM A SELENIUM COMPOUND, A VANILLOID COMPOUND AND A CYTOPLASMIC GLYCOLYSIS REDUCTION AGENT.
• [37] Modification of eukaryotic initiation factor 5A from Plasmodium vivax by a truncated deoxyhypusine synthase from Plasmodium falciparum: An enzyme w... Bioorg Med Chem. 2007 Sep 15;15(18):6200-7.
• [38] Effects of N1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on the growth of tumorigenic cell lines in culture. Biochim Biophys Acta. 1996 Jan 10;1310(1):119-26.
• [39] Synthesis of 2-modified aristeromycins and their analogs as potent inhibitors against Plasmodium falciparum S-adenosyl-L-homocysteine hydrolase. Bioorg Med Chem. 2008 Apr 1;16(7):3809-15.
• [40] Molecular approaches for the treatment of hemorrhagic fever virus infections. Antiviral Res. 1993 Sep;22(1):45-75.
• [41] Design, synthesis, and molecular modeling studies of 5'-deoxy-5'-ureidoadenosine: 5'-ureido group as multiple hydrogen bonding donor in the active ... Bioorg Med Chem Lett. 2007 Aug 15;17(16):4456-9.
• [42] Synthesis of 5'-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5' and sulfur atoms replaced by a vinyl or halovinyl u... Bioorg Med Chem. 2008 May 15;16(10):5424-33.
• [43] Synthesis of 4'-modified noraristeromycins to clarify the effect of the 4'-hydroxyl groups for inhibitory activity against S-adenosyl-L-homocystein... Bioorg Med Chem Lett. 2008 Apr 15;18(8):2615-8.
• [44] Synthesis of 5'-substituted fluoro-neplanocin A analogues: importance of a hydrogen bonding donor at 5'-position for the inhibitory activity of S-a... Bioorg Med Chem Lett. 2004 Nov 15;14(22):5641-4.
• [45] Diversity in enoyl-acyl carrier protein reductases. Cell Mol Life Sci. 2009 May;66(9):1507-17.
• [46] Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7.
• [47] Mechanism of thioamide drug action against tuberculosis and leprosy. J Exp Med. 2007 Jan 22;204(1):73-8.
• [48] Affinium Pharmaceuticals Announces the Initiation of a Phase 1 Intravenous Clinical Trial of a New Antibiotic Prodrug, and the Closing of a Follow-on Financing Round. PR Newswire Sep. 4, 2013 10:16 PM.
• [49] SAR and pharmacophore models for the rhodanine inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase. IUBMB Life. 2010 Mar;62(3):204-13.
• [50] 2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections. Bioorg Med Chem. 2010 Nov 1;18(21):7475-85.
• [51] Targeting NAD biosynthesis in bacterial pathogens. US8785499.
• [52] Crystal structures of E. coli nicotinate mononucleotide adenylyltransferase and its complex with deamido-NAD. Structure. 2002 Jan;10(1):69-79.
• [53] Clinical pipeline report, company report or official report of Roche (2009).
• [54] Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016).Expert Opin Ther Pat. 2017 Jun;27(6):677-690.
• [55] Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase and differentiation induction of K562 cells among the mycoph... Bioorg Med Chem. 2010 Nov 15;18(22):8106-11.
• [56] Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment. J Med Chem. 2007 Dec 27;50(26):6685-91.
• [57] Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase. Bioorg Med Chem. 2008 Aug 1;16(15):7462-9.
• [58] Low molecular weight indole fragments as IMPDH inhibitors. Bioorg Med Chem Lett. 2006 May 1;16(9):2535-8.
• [59] Novel indole inhibitors of IMPDH from fragments: synthesis and initial structure-activity relationships. Bioorg Med Chem Lett. 2006 May 1;16(9):2539-42.
• [60] Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia. J Med Chem. 2002 Jan 31;45(3):703-12.
• [61] Effects of changeover from voglibose to acarbose on postprandial triglycerides in type 2 diabetes mellitus patients. Adv Ther. 2009 Jun;26(6):660-6.
• [62] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [63] Drug therapy of postprandial hyperglycaemia. Drugs. 1999 Jan;57(1):19-29.
• [64] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [65] 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. (Target id: 2627).
• [66] Treatment With Novel Galactomannan Derivative Reduces 2-Hour Postprandial Glucose Excursions in Individuals With Type 2 Diabetes Treated With Oral Medications and/or Insulin. J Diabetes Sci Technol. 2014 September; 8(5): 1018-1022.
• [67] Pathology of perbutylated-N-butyl-1-deoxynojiromycin (an alpha-glucosidase-1 inhibitor) in Sprague-Dawley rats. Toxicol Pathol. 1996 Sep-Oct;24(5):531-8.
• [68] Probing the active-site requirements of human intestinal N-terminal maltase-glucoamylase: Synthesis and enzyme inhibitory activities of a six-membe... Bioorg Med Chem. 2010 Nov 15;18(22):7794-8.
• [69] Identification of novel inhibitors of UDP-Glc 4'-epimerase, a validated drug target for african sleeping sickness. Bioorg Med Chem Lett. 2006 Nov 15;16(22):5744-7.
• [70] Crystal structure of beta1,4-galactosyltransferase complex with UDP-Gal reveals an oligosaccharide acceptor binding site. J Mol Biol. 2002 Apr 26;318(2):491-502.