Details of the Drug

General Information of Drug (ID: DM8M2N3)

Drug Name

GLYCYRRHIZIN

Synonyms

Glycyrrhizic acid; glycyrrhizin; Glycyrrhizinic acid; 1405-86-3; Glycyron; Glycyrrhetinic acid glycoside; glyzyrrhizin; 18-beta-Glycyrrhizic acid; Glycyrrizin; Liquorice; UNII-6FO62043WK; Rizinsan K2 A2 (free acid); HSDB 496; EINECS 215-785-7; C42H62O16; Glycyrrhizin [JAN]; NSC 167409; NSC 234419; BRN 0077922; CHEMBL441687; NSC 2800; beta-Glycyrrhizin; CHEBI:15939; 6FO62043WK; DSSTox_RID_82047; DSSTox_CID_27006; DSSTox_GSID_47006; Glycyram; alpha-D-Glucopyranosiduronic acid, (3beta,20beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-

Indication

Disease Entry	ICD 11	Status	REF
Influenza virus infection	1E30-1E32	Phase 3	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

822.9

Logarithm of the Partition Coefficient (xlogp)

3.7

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Clearance: The total body clearance of drug is 16-25 mL/h/kg [2]
Elimination: About 1.1-2.5% of the administered dose of glycyrrhizic acid can be found in urine which corresponds to the minimal cycling and reabsorption of this compound [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 3.5 hours [3]
Metabolism: The drug is metabolized via the intestinal bacteria for the formation of glycyrrhetinic acid []
Vd: The volume of distribution (Vd) of drug is 0.037-0.064 L/kg [4]

Chemical Identifiers

Formula: C42H62O16
IUPAC Name: (2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
Canonical SMILES: C[C@]12CC[C@](C[C@H]1C3=CC(=O)[C@@H]4[C@]5(CC[C@@H](C([C@@H]5CC[C@]4([C@@]3(CC2)C)C)(C)C)O[C@@H]6[C@@H]([C@H]([C@@H]([C@H](O6)C(=O)O)O)O)O[C@H]7[C@@H]([C@H]([C@@H]([C@H](O7)C(=O)O)O)O)O)C)(C)C(=O)O
InChI: InChI=1S/C42H62O16/c1-37(2)21-8-11-42(7)31(20(43)16-18-19-17-39(4,36(53)54)13-12-38(19,3)14-15-41(18,42)6)40(21,5)10-9-22(37)55-35-30(26(47)25(46)29(57-35)33(51)52)58-34-27(48)23(44)24(45)28(56-34)32(49)50/h16,19,21-31,34-35,44-48H,8-15,17H2,1-7H3,(H,49,50)(H,51,52)(H,53,54)/t19-,21-,22-,23-,24-,25-,26-,27+,28-,29-,30+,31+,34-,35-,38+,39-,40-,41+,42+/m0/s1
InChIKey: LPLVUJXQOOQHMX-QWBHMCJMSA-N

Cross-matching ID

PubChem CID: 14982
ChEBI ID: CHEBI:15939
CAS Number: 1405-86-3
TTD ID: D0T8QB
VARIDT ID: DR00914
INTEDE ID: DR0786

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	TTN7BL9	DHI1_HUMAN	Inhibitor	[5]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 3 (ABCC3)	DTQ3ZHF	MRP3_HUMAN	Substrate	[6]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[7]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[8]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[8]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Gene/Protein Processing	[9]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Protein Interaction/Cellular Processes	[10]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[11]
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Gene/Protein Processing	[11]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[12]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Gene/Protein Processing	[9]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[11]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[11]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Gene/Protein Processing	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Influenza virus infection

ICD Disease Classification

1E30-1E32

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	DTT	HSD11B1	2.03E-01	-0.01	-0.08
Multidrug resistance-associated protein 3 (ABCC3)	DTP	MRP3	9.87E-01	-1.86E-01	-4.71E-01
Multidrug resistance-associated protein 2 (ABCC2)	DTP	MRP2	7.65E-01	-2.63E-02	-1.32E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	8.58E-01	-3.73E-03	-1.00E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.76E-01	-4.64E-01	-9.16E-01

Molecular Expression Atlas (MEA)

MEA Detail

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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: 4688).
2	Ploeger B, Mensinga T, Sips A, Seinen W, Meulenbelt J, DeJongh J: The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Drug Metab Rev. 2001 May;33(2):125-47. doi: 10.1081/DMR-100104400 .
3	Analysis and pharmacokinetics of glycyrrhizic acid and glycyrrhetinic acid in humans and experimental animals. Steroids. 1994 Feb;59(2):121-6.
4	Yamamura Y, Kawakami J, Santa T, Kotaki H, Uchino K, Sawada Y, Tanaka N, Iga T: Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high-performance liquid chromatographic method. J Pharm Sci. 1992 Oct;81(10):1042-6.
5	Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1 inhibitor for the treatment of diabetes. Bioorg Med Chem. 2009 Aug 1;17(15):5722-32.
6	The combination of glycyrrhizin and lamivudine can reverse the cisplatin resistance in hepatocellular carcinoma cells through inhibition of multidrug resistance-associated proteins. Int J Oncol. 2007 Dec;31(6):1465-72.
7	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8	Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010 Aug;66(8):805-810.
9	Verbascoside inhibits the epithelial-mesenchymal transition of prostate cancer cells through high-mobility group box 1/receptor for advanced glycation end-products/TGF- pathway. Environ Toxicol. 2021 Jun;36(6):1080-1089. doi: 10.1002/tox.23107. Epub 2021 Feb 1.
10	Identifying environmental chemicals as agonists of the androgen receptor by using a quantitative high-throughput screening platform. Toxicology. 2017 Jun 15;385:48-58. doi: 10.1016/j.tox.2017.05.001. Epub 2017 May 4.
11	Antiproliferative and apoptotic potential of Glycyrrhizin against HPV16+?Caski cervical cancer cells: A plausible association with downreguation of HPV E6 and E7 oncogenes and Notch signaling pathway. Saudi J Biol Sci. 2022 May;29(5):3264-3275. doi: 10.1016/j.sjbs.2022.01.054. Epub 2022 Jan 31.
12	Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.