Details of the Drug

General Information of Drug (ID: DMI3491)

• Drug Name: Apigenin
• Synonyms: apigenin; 520-36-5; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one; Chamomile; Versulin; Spigenin; Apigenol; 4',5,7-Trihydroxyflavone; Apigenine; C.I. Natural Yellow 1; 5,7,4'-Trihydroxyflavone; Pelargidenon 1449; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4-benzopyrone; 2-(p-Hydroxyphenyl)-5,7-dihydroxychromone; UCCF 031; NSC 83244; UNII-7V515PI7F6; 5,7-Dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one; CCRIS 3789; CHEBI:18388; CHEMBL28; EINECS 208-292-3; 4H-1-Benzopyran-4-one, 5,7-di

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 270.24
  Topological Polar Surface Area (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: 5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
  Canonical SMILES: C1=CC(=CC=C1C2=CC(=O)C3=C(C=C(C=C3O2)O)O)O
  InChI: InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)13-7-12(19)15-11(18)5-10(17)6-14(15)20-13/h1-7,16-18H
  InChIKey: KZNIFHPLKGYRTM-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5280443
  ChEBI ID: CHEBI:18388
  CAS Number: 520-36-5
  DrugBank ID: DB07352
  TTD ID: D00RIX
  VARIDT ID: DR00822

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aldose reductase (AKR1B1)	TTFBNVI	ALDR_HUMAN	Inhibitor	[2]
Androgen receptor messenger RNA (AR mRNA)	TTKPW01	ANDR_HUMAN	Inhibitor	[3]
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[4]
Casein kinase II alpha (CSNK2A1)	TTER6YH	CSK21_HUMAN	Inhibitor	[5]
Cyclin-dependent kinase 6 (CDK6)	TTO0FDJ	CDK6_HUMAN	Inhibitor	[6]
Cytochrome P450 1B1 (CYP1B1)	TTI84H7	CP1B1_HUMAN	Inhibitor	[7]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)	TTIWB6L	DHB1_HUMAN	Inhibitor	[8]
Influenza Neuraminidase (Influ NA)	TT50QJ3	NRAM_I33A0	Inhibitor	[9]
Plasmodium CDK Pfmrk (Malaria Pfmrk)	TTSFWA7	P90584_PLAFA	Inhibitor	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Aldose reductase (AKR1B1)	DTT	AKR1B1	1.08E-20	0.94	1.58

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: 4136).
• [2] Erigeroflavanone, a flavanone derivative from the flowers of Erigeron annuus with protein glycation and aldose reductase inhibitory activity. J Nat Prod. 2008 Apr;71(4):713-5.
• [3] Effect of flavonoids on androgen and glucocorticoid receptors based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4706-10.
• [4] Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
• [5] Structural insight into human CK2alpha in complex with the potent inhibitor ellagic acid. Bioorg Med Chem Lett. 2009 Jun 1;19(11):2920-3.
• [6] Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. J Med Chem. 2005 Feb 10;48(3):737-43.
• [7] Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
• [8] 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.
• [9] Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem. 2009 Oct 1;17(19):6816-23.
• [10] A three-dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclin-dependent kinases and discovery of different class... J Med Chem. 2004 Oct 21;47(22):5418-26.
• [11] Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases, Bioorg. Med. Chem. Lett. 20(13):3863-3867 (2010).
• [12] Selective inhibition of Pfmrk, a Plasmodium falciparum CDK, by antimalarial 1,3-diaryl-2-propenones. Bioorg Med Chem Lett. 2009 Apr 1;19(7):1982-5.
• [13] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [14] Evaluation of broad spectrum protein kinase inhibitors to probe the architecture of the malarial cyclin dependent protein kinase Pfmrk. Bioorg Med Chem Lett. 2007 Sep 1;17(17):4961-6.
• [15] Effective aromatase inhibition by anastrozole in a patient with gonadotropin-independent precocious puberty in McCune-Albright syndrome. J Pediatr Endocrinol Metab. 2002;15 Suppl 3:945-8.
• [16] Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
• [17] Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis. Chem Res Toxicol. 2007 Jul;20(7):1038-45.
• [18] Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J Med Chem. 2005 Nov 17;48(23):7282-9.
• [19] Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9.
• [20] Toremifene-atamestane; alone or in combination: predictions from the preclinical intratumoral aromatase model. J Steroid Biochem Mol Biol. 2008 Jan;108(1-2):1-7.
• [21] Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. J Med Chem. 2010 Mar 11;53(5):2155-70.
• [22] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [23] Long-term effect of epalrestat, an aldose reductase inhibitor, on the development of incipient diabetic nephropathy in Type 2 diabetic patients. J Diabetes Complications. 2001 Sep-Oct;15(5):241-4.
• [24] Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.
• [25] Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study. Diabetes Care. 2001 Oct;24(10):1776-82.
• [26] 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: 2768).
• [27] Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes. J Nat Prod. 1996 Apr;59(4):443-5.
• [28] ClinicalTrials.gov (NCT02332005) 12-Month Efficacy and Safety of Diepalrestat in Adults With Diabetic Peripheral Neuropathy, a DB, Placebo-Controlled Study (DE-DPN). U.S. National Institutes of Health.
• [29] Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors ... J Med Chem. 2005 May 5;48(9):3141-52.
• [30] A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. J Diabetes Complications. 2005 Sep-Oct;19(5):247-53.
• [31] Effects of novel aldose reductase inhibitors, M16209 and M16287, on streptozotocin-induced diabetic neuropathy in rats. Eur J Pharmacol. 1991 Feb 7;193(2):185-91.
• [32] Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102.
• [33] Developing new antiviral agents for influenza treatment: what does the future hold Clin Infect Dis. 2009 Jan 1;48 Suppl 1:S3-13.
• [34] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [35] Inhibition of neuraminidase inhibitor-resistant influenza virus by DAS181, a novel sialidase fusion protein. PLoS One. 2009 Nov 6;4(11):e7838.
• [36] US patent application no. 2010,0081,713, Compositions and methods for treating viral infections.
• [37] CN patent application no. 104447481, Benzoic acid thiourea anti-influenza virus compounds as well as preparation method and use thereof.
• [38] 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.
• [39] 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.
• [40] 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.
• [41] 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: 628).
• [42] Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist. J Med Chem. 2000 Dec 28;43(26):5010-6.
• [43] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [44] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
• [45] 2011 Pipeline of Santaris Pharma.
• [46] Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4.
• [47] Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen recepto... J Med Chem. 2008 Nov 13;51(21):7010-4.
• [48] Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9.
• [49] Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A. J Med Chem. 1996 Dec 20;39(26):5215-27.
• [50] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [51] Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo. ACS Med Chem Lett. 2013 Jul 3;4(8):800-5.
• [52] Adenosine-5'-carboxylic acid peptidyl derivatives as inhibitors of protein kinases. Bioorg Med Chem Lett. 1999 May 17;9(10):1447-52.
• [53] CK2alpha and CK2alpha' subunits differ in their sensitivity to 4,5,6,7-tetrabromo- and 4,5,6,7-tetraiodo-1H-benzimidazole derivatives. Eur J Med Chem. 2012 Jan;47(1):345-50.
• [54] Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.
• [55] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [56] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
• [57] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [58] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [59] Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013 Nov 15;19(22):6173-82.
• [60] Clinical pipeline report, company report or official report of Gan & Lee Pharmaceuticals.
• [61] Clinical pipeline report, company report or official report of Fochon Pharmaceuticals.
• [62] Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
• [63] Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors. J Med Chem. 2002 Jan 3;45(1):160-4.