Details of the Drug

General Information of Drug (ID: DM8YMWE)

Drug Name
Riboflavin
Synonyms
riboflavin; vitamin B2; Lactoflavin; Riboflavine; Vitamin G; 83-88-5; Lactoflavine; (-)-riboflavin; Beflavine; Beflavin; Riboflavina; Flavaxin; Vitaflavine; Riboflavinum; Ribocrisina; Ribovel; Lactobene; Ribotone; Flaxain; Ribosyn; Riboderm; Ribipca; Flavin BB; Vitasan B2; Fiboflavin; Dermadram; Hyflavin; HYRE; Vitamin Bi; Aqua-Flave; 7,8-Dimethyl-10-ribitylisoalloxazine; Russupteridine Yellow III; 6,7-Dimethyl-9-D-ribitylisoalloxazine; Riboflavinequinone; Riboflavinum [INN-Latin]; Riboflavine [INN-French]; Riboflavina [INN-Spanish]
Indication
Disease Entry ICD 11 Status REF
Acne vulgaris ED80 Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 376.4
Topological Polar Surface Area (xlogp) -1.5
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 5
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
Elimination
75% of drug is excreted from urine in the unchanged form [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 66 - 84 minutes [4]
Metabolism
The drug is metabolized via the hepatic [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.32847 micromolar/kg/day [6]
Water Solubility
The ability of drug to dissolve in water is measured as 0.11 mg/mL [3]
Chemical Identifiers
Formula
C17H20N4O6
IUPAC Name
7,8-dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]benzo[g]pteridine-2,4-dione
Canonical SMILES
CC1=CC2=C(C=C1C)N(C3=NC(=O)NC(=O)C3=N2)C[C@@H]([C@@H]([C@@H](CO)O)O)O
InChI
InChI=1S/C17H20N4O6/c1-7-3-9-10(4-8(7)2)21(5-11(23)14(25)12(24)6-22)15-13(18-9)16(26)20-17(27)19-15/h3-4,11-12,14,22-25H,5-6H2,1-2H3,(H,20,26,27)/t11-,12+,14-/m0/s1
InChIKey
AUNGANRZJHBGPY-SCRDCRAPSA-N
Cross-matching ID
PubChem CID
493570
ChEBI ID
CHEBI:17015
CAS Number
83-88-5
DrugBank ID
DB00140
TTD ID
D04QST
VARIDT ID
DR00079
INTEDE ID
DR1416

Molecular Interaction Atlas of This Drug


Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Riboflavin transporter 2 (SLC52A3) DTBVQIO S52A3_HUMAN Substrate [7]
Riboflavin transporter 3 (SLC52A2) DTAVOS6 S52A2_HUMAN Substrate [7]
Riboflavin transporter 1 (SLC52A1) DT7NOKR S52A1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [9]
Eosinophil peroxidase (EPX) DETE84Z PERE_HUMAN Substrate [10]
Tartrate-resistant acid ATPase (ACP5) DESITDW PPA5_HUMAN Substrate [10]
Xylosyl phosphatase (PXYLP1) DEGSUI0 PXYP1_HUMAN Substrate [10]
Prostatic acid phosphatase (ACP3) DEDW5H6 PPAP_HUMAN Substrate [10]
Acid phosphatase-like protein 1 (ACP6) DER6BCE PPA6_HUMAN Substrate [10]
NADPH-dependent oxidoreductase (nfrA) DE82GV7 NRFA_STAA8 Substrate [11]
NADPH-dependent nitroreductase (nfrA1) DE21PLI NFRA1_BACSU Substrate [12]
Nitroreductase (NTR) DE0K82S A0A5K1UB29_SALTM Substrate [13], [14]
Testicular acid phosphatase (ACP4) DE3OZT4 PPAT_HUMAN Substrate [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

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2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3 BDDCS applied to over 900 drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
6 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
7 An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Mol Genet Metab. 2017 Dec;122(4):182-188.
8 Multidrug transporter ABCG2/breast cancer resistance protein secretes riboflavin (vitamin B2) into milk. Mol Cell Biol. 2007 Feb;27(4):1247-53.
9 Disruption of endogenous regulator homeostasis underlies the mechanism of rat CYP1A1 mRNA induction by metyrapone. Biochem J. 1998 Apr 1;331 ( Pt 1):273-81.
10 An atlas of human metabolism. Sci Signal. 2020 Mar 24;13(624). pii: eaaz1482. (Reaction HMR_6507)
11 Reduction of polynitroaromatic compounds: the bacterial nitroreductases. FEMS Microbiol Rev. 2008 May;32(3):474-500.
12 Conversion of NfsA, the major Escherichia coli nitroreductase, to a flavin reductase with an activity similar to that of Frp, a flavin reductase in Vibrio harveyi, by a single amino acid substitution. J Bacteriol. 1998 Jan;180(2):422-5.
13 Purification and characterization of wild-type and mutant "classical" nitroreductases of Salmonella typhimurium. L33R mutation greatly diminishes binding of FMN to the nitroreductase of S. typhimurium. J Biol Chem. 1998 Sep 11;273(37):23922-8.
14 Prenatal diagnosis of junctional epidermolysis bullosa Herlitz type. Lancet. 1989 Oct 28;2(8670):1035-6. Letter
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16 Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74.
17 Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94.
18 Preferred orientations in the binding of 4'-hydroxyacetanilide (acetaminophen) to cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation studies. J Med Chem. 1994 Mar 18;37(6):860-7.
19 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
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21 A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med. 2005;43(7):702-6.
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23 Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab. 2007 Aug;8(6):554-62.
24 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
25 CYP1A1 and Cnr nitroreductase bioactivated niclosamide in vitro. Mutagenesis. 2013 Nov;28(6):645-51.
26 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
27 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
28 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
29 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
30 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
31 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
32 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
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