Details of the Drug

General Information of Drug (ID: DMUPE07)

• Drug Name: Nicotinamide
• Synonyms: Aminicotin; Amixicotyn; Amnicotin; Benicot; Dipegyl; Endobion; Enduramide; Hansamid; Mediatric; Niacevit; Niacinamide; Niacotinamide; Niamide; Nicamina; Nicamindon; Nicasir; Nicobion; Nicofort; Nicogen; Nicomidol; Nicosylamide; Nicota; Nicotamide; Nicotilamide; Nicotililamido; Nicotinamid; Nicotinamida; Nicotinamidum; Nicotinsaeureamid; Nicotinsaureamid; Nicotol; Nicotylamide; Nicotylamidum; Nicovit; Nicovitina; Nicovitol; Nicozymin; Nikasan; Nikazan; Nikotinamid; Nikotinsaeureamid; Niocinamide; Niozymin; Papulex; Pelmin; Pelmine; Savacotyl; Amid kyseliny nikotinove; Amid kyseliny nikotinove [Czech]; Amide PP; Astra Brand of Niacinamide; Austrovit PP; Delonin amide; Factor pp; Inovitan PP; Jenapharm Brand of Niacinamide; Merck Brand of Niacinamide; Niacinamide Astra Brand; Niacinamide Jenapharm Brand; Niacinamide Merck Brand; Niacinamide Pharmagenix Brand; Niacinamide [USAN]; Niavit PP; Nicotine acid amide; Nicotine amide; Nicotinic acid amide; Nicotinic amide; Nicotinsaureamid Jenapharm; Nicotinsaureamid [German]; Nikotinsaeureamid [German]; Pelonin amide; Pharmagenix Brand of Niacinamide; Vitamin B; Vitamin PP; Witamina PP; Nicosan 2; Vitamin H1; B 3, Vitamin; B3, Vitamin; Beta-Pyridinecarboxamide; Jenapharm, Nicotinsaureamid; Nandervit-N; Niacin-Vitamin B3; Niacinamide (USP); Nicotinamida [INN-Spanish]; Nicotinamide (Niacinamide); Nicotinamidum [INN-Latin]; Niko-tamin; PP-Faktor; Vi-Nicotyl; Vitamin B (VAN); M-(Aminocarbonyl)pyridine; Niacinamide, Nicotinic acid amide, Nicotinamide; Nicotinamide (JP15/INN); Nicotinamide, niacin, vitamin B3; Nicotinamide-carbonyl-14C; Pyridine-3-carboxamide; Pyridine-3-carboxylic acid amide; 3 Pyridinecarboxamide; 3-Carbamoylpyridine; 3-Pyridinecarboxamide; 3-Pyridinecarboxylic acid amide

Indication

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[1]
Clear cell renal carcinoma	N.A.	Approved	[2]
Inflammatory skin condition	EF20.Y	Approved	[3]
Pellagra	N.A.	Approved	[4]
Primary hypercholesterolemia	5C80.00	Approved	[5]
Psoriasis	EA90	Approved	[6]
Thyroid cancer	2D10	Approved	[7]

• Therapeutic Class: Antiinflammatory Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 122.12
  Logarithm of the Partition Coefficient (xlogp); -0.4
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [8]
  Water Solubility: The ability of drug to dissolve in water is measured as 1000 mg/mL [8]
• Chemical Identifiers:
  Formula: C6H6N2O
  IUPAC Name: pyridine-3-carboxamide
  Canonical SMILES: C1=CC(=CN=C1)C(=O)N
  InChI: InChI=1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9)
  InChIKey: DFPAKSUCGFBDDF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 936
  ChEBI ID: CHEBI:17154
  CAS Number: 98-92-0
  DrugBank ID: DB02701
  TTD ID: D06NVJ
  INTEDE ID: DR1147
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Poly [ADP-ribose] polymerase 1 (PARP1)	TTVDSZ0	PARP1_HUMAN	Binder	[9]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2E1 (CYP2E1) Main DME	DEVDYN7	CP2E1_HUMAN	Substrate	[10]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Post-Translational Modifications	[11]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[12]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Gene/Protein Processing	[13]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Gene/Protein Processing	[13]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Gene/Protein Processing	[14]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Gene/Protein Processing	[15]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Protein Interaction/Cellular Processes	[16]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[17]
Chimeric ERCC6-PGBD3 protein (ERCC6)	OT2QZKSF	ERPG3_HUMAN	Regulation of Drug Effects	[18]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[17]

Molecular Expression Atlas of This Drug

• The Studied Disease: Acne vulgaris
• ICD Disease Classification: ED80

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Poly [ADP-ribose] polymerase 1 (PARP1)	DTT	PARP1	5.01E-05	1.02	2.68
Cytochrome P450 2E1 (CYP2E1)	DME	CYP2E1	8.79E-01	-8.17E-02	-6.97E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Nicotinamide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Nicotinamide and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[19]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Nicotinamide and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[20]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Nicotinamide and Cannabidiol.	Epileptic encephalopathy [8A62]	[21]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Nicotinamide and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[22]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Nicotinamide and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[23]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Nicotinamide and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[24]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Nicotinamide and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[25]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Nicotinamide and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[26]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Nicotinamide and Idelalisib.	Mature B-cell leukaemia [2A82]	[19]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Nicotinamide and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[21]

References

• [1] The role of nicotinamide in acne treatment. Dermatol Ther. 2017 Sep;30(5).
• [2] ABAT and ALDH6A1, regulated by transcription factor HNF4A, suppress tumorigenic capability in clear cell renal cell carcinoma. J Transl Med. 2020 Feb 24;18(1):101.
• [3] 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: 1588).
• [4] Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation. Antioxidants (Basel). 2021 Aug 21;10(8):1315.
• [5] Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Hypertensive Patients With Primary Hyperaldosteronemia: Role of 5,6,7,8-Tetrahydrobiopterin Oxidation and Endothelial Nitric Oxide Synthase Uncoupling. Hypertension. 2016 Feb;67(2):430-9.
• [6] Co-delivery of methotrexate and nicotinamide by cerosomes for topical psoriasis treatment with enhanced efficacy. Int J Pharm. 2021 Aug 10;605:120826.
• [7] Nicotinamide N-Methyltransferase in Head and Neck Tumors: A Comprehensive Review. Biomolecules. 2021 Oct 28;11(11):1594.
• [8] BDDCS applied to over 900 drugs
• [9] beta-1,2,3-Triazolyl-nucleosides as nicotinamide riboside mimics. Nucleosides Nucleotides Nucleic Acids. 2009 Mar;28(3):238-59.
• [10] Nicotinamide N-oxidation by CYP2E1 in human liver microsomes. Drug Metab Dispos. 2013 Mar;41(3):550-3.
• [11] Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells. Biochem Biophys Res Commun. 2009 Jan 23;378(4):836-41. doi: 10.1016/j.bbrc.2008.11.130. Epub 2008 Dec 9.
• [12] SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity. J Cell Physiol. 2007 Jan;210(1):161-6. doi: 10.1002/jcp.20831.
• [13] Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells. Toxicol Appl Pharmacol. 2016 Jan 15;291:70-83. doi: 10.1016/j.taap.2015.12.006. Epub 2015 Dec 19.
• [14] Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation. Transplantation. 2003 Nov 15;76(9):1285-8. doi: 10.1097/01.TP.0000098905.86445.0F.
• [15] Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells. Clin Exp Immunol. 2012 Apr;168(1):113-24. doi: 10.1111/j.1365-2249.2011.04549.x.
• [16] Sirtuin-1 (SIRT1) is required for promoting chondrogenic differentiation of mesenchymal stem cells. J Biol Chem. 2014 Aug 8;289(32):22048-62. doi: 10.1074/jbc.M114.568790. Epub 2014 Jun 24.
• [17] The effect of tertiary butylhydroperoxide and nicotinamide on human cortical neurons. Neurotoxicology. 2003 Jun;24(3):443-8. doi: 10.1016/S0161-813X(03)00019-6.
• [18] A high-fat diet and NAD(+) activate Sirt1 to rescue premature aging in cockayne syndrome. Cell Metab. 2014 Nov 4;20(5):840-855. doi: 10.1016/j.cmet.2014.10.005. Epub 2014 Nov 4.
• [19] Product Information. Hivid (zalcitabine). Roche Laboratories, Nutley, NJ.
• [20] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [21] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [22] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
• [23] Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
• [24] Canadian Pharmacists Association.
• [25] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
• [26] Bodmer M, Sulz M, Stadlmann S, Droll A, Terracciano L, Krahenbuhl S "Fatal liver failure in an adult patient with acute lymphoblastic leukemia following treatment with L-asparaginase." Digestion 74 (2006): epub. [PMID: 16988508]