Details of the Drug

General Information of Drug (ID: DM4C7E6)

• Drug Name: BAICALEIN
• Synonyms: baicalein; 491-67-8; 5,6,7-Trihydroxyflavone; 5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one; Noroxylin; Biacalein; BaiKalein; Baicelein; UNII-49QAH60606; NSC661431; NSC 661431; CHEMBL8260; 5,6,7-trihydroxy-2-phenylchromen-4-one; CHEBI:2979; FXNFHKRTJBSTCS-UHFFFAOYSA-N; MFCD00017459; 4H-1-Benzopyran-4-one, 5,6,7-trihydroxy-2-phenyl-; 49QAH60606; 5,7-Trihydroxyflavone; 5,6,7-trihydroxy-2-phenyl-chromen-4-one; Sho-saiko-to; SMR000112462; SR-01000597499; Baicalein, 8; Baicalein,(S); 3WL; Baicalein, 14; Baicalein, 98%; AC1NQYPP; Tocris-1761

Indication

Disease Entry	ICD 11	Status	REF
Influenza virus infection	1E30-1E32	Phase 2	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 270.24
  Logarithm of the Partition Coefficient (xlogp); 1.7
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C15H10O5
  IUPAC Name: 5,6,7-trihydroxy-2-phenylchromen-4-one
  Canonical SMILES: C1=CC=C(C=C1)C2=CC(=O)C3=C(O2)C=C(C(=C3O)O)O
  InChI: InChI=1S/C15H10O5/c16-9-6-11(8-4-2-1-3-5-8)20-12-7-10(17)14(18)15(19)13(9)12/h1-7,17-19H
  InChIKey: FXNFHKRTJBSTCS-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5281605
  ChEBI ID: CHEBI:2979
  CAS Number: 491-67-8
  DrugBank ID: DB16101
  TTD ID: D00YEV

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Inhibitor	[2]
L-selectin (SELL)	TT2IYXF	LYAM1_HUMAN	Inhibitor	[3]
Lactoylglutathione lyase (GLO1)	TTV9A7R	LGUL_HUMAN	Inhibitor	[4]
P-selectin (SELP)	TTE5VG0	LYAM3_HUMAN	Inhibitor	[3]
Prolyl endopeptidase (PREP)	TTNGKET	PPCE_HUMAN	Inhibitor	[5]
Tumor necrosis factor (TNF)	TTF8CQI	TNFA_HUMAN	Inhibitor	[6]
Xanthine dehydrogenase/oxidase (XDH)	TT7RJY8	XDH_HUMAN	Inhibitor	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[8]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Gene/Protein Processing	[9]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Gene/Protein Processing	[10]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[11]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[12]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Gene/Protein Processing	[13]
Arylamine N-acetyltransferase 1 (NAT1)	OTCCNQ3H	ARY1_HUMAN	Gene/Protein Processing	[14]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[15]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[16]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[11]

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
Prolyl endopeptidase (PREP)	DTT	PREP	5.70E-01	-0.09	-0.33

References

• [1] ClinicalTrials.gov (NCT03830684) A Randomized, Double-blind, Placebo-controlled, Multicenter and Phase IIa Clinical Trial for the Effectiveness and Safety of Baicalein Tablets in the Treatment of Improve Other Aspects of Healthy Adult With Influenza Fever. U.S. National Institutes of Health.
• [2] Indazolinones, a new series of redox-active 5-lipoxygenase inhibitors with built-in selectivity and oral activity. J Med Chem. 1991 Mar;34(3):1028-36.
• [3] Rational design of novel, potent small molecule pan-selectin antagonists. J Med Chem. 2007 Mar 22;50(6):1101-15.
• [4] Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorg Med Chem. 2008 Apr 1;16(7):3969-75.
• [5] Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor. Bioorg Med Chem. 2008 Aug 1;16(15):7516-24.
• [6] Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening. Bioorg Med Chem Lett. 2010 Nov 1;20(21):6195-8.
• [7] Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
• [8] Effect of the interaction between lipoxygenase pathway and progesterone on the regulation of hydroxysteroid 11-Beta dehydrogenase 2 in cultured human term placental trophoblasts. Biol Reprod. 2008 Mar;78(3):514-20.
• [9] Baicalein inhibits the migration and invasive properties of human hepatoma cells. Toxicol Appl Pharmacol. 2011 Sep 15;255(3):316-26. doi: 10.1016/j.taap.2011.07.008. Epub 2011 Jul 23.
• [10] Baicalein represses TGF-1-induced fibroblast differentiation through the inhibition of miR-21. Toxicol Appl Pharmacol. 2018 Nov 1;358:35-42. doi: 10.1016/j.taap.2018.09.007. Epub 2018 Sep 7.
• [11] The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells. Toxicol Appl Pharmacol. 2011 Aug 1;254(3):221-8. doi: 10.1016/j.taap.2011.03.016. Epub 2011 Mar 30.
• [12] MiR-3663-3p participates in the anti-hepatocellular carcinoma proliferation activity of baicalein by targeting SH3GL1 and negatively regulating EGFR/ERK/NF-B signaling. Toxicol Appl Pharmacol. 2021 Jun 1;420:115522. doi: 10.1016/j.taap.2021.115522. Epub 2021 Apr 8.
• [13] Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Environ Health Perspect. 2003 Dec;111(16):1877-82.
• [14] N-acetyltransferase is involved in baicalein-induced N-acetylation of 2-aminofluorene and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells. In Vivo. 2005 Mar-Apr;19(2):399-405.
• [15] Structure-activity relationship and mechanism of flavonoids on the inhibitory activity of P-glycoprotein (P-gp)-mediated transport of rhodamine123 and daunorubicin in P-gp overexpressed human mouth epidermal carcinoma (KB/MDR) cells. Food Chem Toxicol. 2021 Sep;155:112381. doi: 10.1016/j.fct.2021.112381. Epub 2021 Jul 1.
• [16] Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT. Mol Cancer Ther. 2007 Nov;6(11):3039-48. doi: 10.1158/1535-7163.MCT-07-0281.