Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMHAZLM)

• Drug Name: NARINGENIN Drug Info
• Synonyms: naringenin; 5,7-Dihydroxy-2-(4-hydroxyphenyl)chroman-4-one; 67604-48-2; 4',5,7-Trihydroxyflavanone; Naringenine; (+/-)-Naringenin; naringetol; 480-41-1; salipurpol; (-)-Naringenin; NARIGENIN; Salipurol; 5,7,4'-Trihydroxyflavanone; 93602-28-9; (S)-Naringenin; BE-14348A; NSC 34875; ( inverted exclamation markA)-Naringenin; CHEMBL32571; MLS000738094; MLS000028739; CHEBI:50202; Flavanone, 4',5,7-trihydroxy-; FTVWIRXFELQLPI-UHFFFAOYSA-N; NSC34875; NSC11855; MFCD00006844; SMR000059039; AK122638; NSC 11855; 4',7-Trihydroxyflavanone
• Cross-matching ID:
  PubChem CID: 932
  ChEBI ID: CHEBI:50202
  CAS Number: CAS 67604-48-2
  TTD Drug ID: DMHAZLM
  VARIDT Drug ID: DR00833
  INTEDE Drug ID: DR2246

Molecule-Related Drug Atlas

Drug(s) Targeting Aromatase (CYP19A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anastrozole	DMNP60F	Breast cancer	2C60-2C65	Approved	[9]
Letrozole	DMH07Y3	Estrogen-receptor positive breast cancer		Approved	[10]
Exemestane	DM9HPW3	Hormonally-responsive breast cancer	2C60-2C65	Approved	[10]
Aminoglutethimide	DMWFHMZ	Cushing disease	5A70	Approved	[11]
FADROZOLE	DM3C5GZ	Breast cancer	2C60-2C65	Approved	[12]
Testolactone	DMVY4GN	Breast cancer	2C60-2C65	Approved	[13]
LIAROZOLE	DM4OYXE	Dermatological disease	DA24.Y	Phase 2/3	[1]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[14]
BGS-649	DMO4MNQ	Endometriosis	GA10	Phase 2	[15]
FORMESTANE	DMWIDJK	Breast cancer	2C60-2C65	Withdrawn from market	[16]

Drug(s) Targeting Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[17]
2'-Monophosphoadenosine 5'-Diphosphoribose	DME9S8M	Discovery agent	N.A.	Investigative	[17]
APIGENIN	DMI3491	Discovery agent	N.A.	Investigative	[3]
KAEMPFEROL	DMHEMUB	Discovery agent	N.A.	Investigative	[3]
4-ANDROSTENE-3-17-DIONE	DMSE8NU	Discovery agent	N.A.	Investigative	[17]
6-(3-Hydroxy-phenyl)-naphthalen-2-ol	DMH8WA2	Discovery agent	N.A.	Investigative	[18]
7-(3-Hydroxy-phenyl)-naphthalen-2-ol	DM2I91C	Discovery agent	N.A.	Investigative	[19]
NSC-94258	DM6VY3P	Discovery agent	N.A.	Investigative	[3]
4-[5-(3-Hydroxyphenyl)-3-thienyl]-2-methylphenol	DM7ERYJ	Discovery agent	N.A.	Investigative	[20]
6-(4-Hydroxy-phenyl)-naphthalen-1-ol	DM2V9XI	Discovery agent	N.A.	Investigative	[19]

Drug(s) Targeting Estrogen receptor beta (ESR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Conjugated Estrogens	DMLT0E1	Dyspareunia	GA12	Approved	[21]
Trilostane	DMQZ9GF	Cushing disease	5A70	Approved	[22]
ARZOXIFENE	DMOKCVI	Breast cancer	2C60-2C65	Approved	[23]
Estrogen	DMGY0UT	Menopause symptom	GA30.0	Approved	[24]
MF-101	DM8Z0I3	Hepatitis virus infection	1E50-1E51	Phase 3	[25]
Genistein	DM0JETC	Menopause symptom	GA30.0	Phase 2/3	[26]
AUS-131	DMUXO3Z	Hot flushes	GA30	Phase 2	[27]
ERB-041	DMCEPUA	Inflammatory bowel disease	DD72	Phase 2	[28]
Erteberel	DMU1XZD	Prostate hyperplasia	GA90	Phase 2	[29]
VG-101	DMAN21O	Menopause symptom	GA30.0	Phase 1/2	[30]

Drug(s) Targeting Lactoylglutathione lyase (GLO1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAICALEIN	DM4C7E6	Influenza virus infection	1E30-1E32	Phase 2	[5]
2-Sulfhydryl-Ethanol	DMJBO3D	Discovery agent	N.A.	Investigative	[31]
KAEMPFEROL	DMHEMUB	Discovery agent	N.A.	Investigative	[5]
S-(N-butyl-N-hydroxycarbamoyl)glutathione	DMU7EQV	Discovery agent	N.A.	Investigative	[32]
S-(N-heptyl-N-hydroxycarbamoyl)glutathione	DMV6T1Q	Discovery agent	N.A.	Investigative	[32]
S-(N-propyl-N-hydroxycarbamoyl)glutathione	DMRFKZ6	Discovery agent	N.A.	Investigative	[32]
S-(N-Hydroxy-N-Iodophenylcarbamoyl)Glutathione	DM1AHIW	Discovery agent	N.A.	Investigative	[31]
S-(N-pentyl-N-hydroxycarbamoyl)glutathione	DM4E9J2	Discovery agent	N.A.	Investigative	[32]
S-(N-methyl-N-hydroxycarbamoyl)glutathione	DM1C9W3	Discovery agent	N.A.	Investigative	[32]
S-(N-4bromophenyl-N-hydroxycarbamoyl)glutathione	DM3FXPV	Discovery agent	N.A.	Investigative	[32]

Drug(s) Targeting Cytochrome P450 1B1 (CYP1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PINOCEMBRIN	DM96VWD	N. A.	N. A.	Phase 2	[2]
Chrysin	DM7V2LG	Discovery agent	N.A.	Investigative	[2]
APIGENIN	DMI3491	Discovery agent	N.A.	Investigative	[2]
KAEMPFEROL	DMHEMUB	Discovery agent	N.A.	Investigative	[2]
ISORHAMNETIN	DMQ4Z6E	Discovery agent	N.A.	Investigative	[2]
ACACETIN	DMQOB0X	Discovery agent	N.A.	Investigative	[2]
TRISMETHOXYRESVERATROL	DM6USPC	Discovery agent	N.A.	Investigative	[33]
Galangin	DM5TQ2O	Discovery agent	N.A.	Investigative	[2]
CHRYSOERIOL	DM96ECL	Discovery agent	N.A.	Investigative	[2]
DIOSMETIN	DM4KXIM	Discovery agent	N.A.	Investigative	[2]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[34]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[35]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[36]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[37]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[36]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[36]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[38]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[36]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[39]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[40]

Drug(s) Metabolized By Cytochrome P450 105D7 (cyp105)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[7]
Mevastatin	DM1LGKP	N. A.	N. A.	Terminated	[7]
Q-27137207	DML5KMT	N. A.	N. A.	Investigative	[7] , [8]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[1]
Cytochrome P450 1B1 (CYP1B1)	TTI84H7	CP1B1_HUMAN	Inhibitor	[2]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)	TTIWB6L	DHB1_HUMAN	Inhibitor	[3]
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Inhibitor	[4]
Lactoylglutathione lyase (GLO1)	TTV9A7R	LGUL_HUMAN	Inhibitor	[5]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 105D7 (cyp105) Main DME	DECV2ME	CYP28_STRAW	Substrate	[7] , [8]

References

• [1] 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.
• [2] Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
• [3] 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.
• [4] Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen re... J Med Chem. 2006 Dec 14;49(25):7357-65.
• [5] 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.
• [6] Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004 Mar 1;36(5):592-604.
• [7] The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
• [8] Hydroxylation of Compactin (ML-236B) by CYP105D7 (SAV_7469) from Streptomyces avermitilis. J Microbiol Biotechnol. 2017 May 28;27(5):956-964.
• [9] 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.
• [10] Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
• [11] Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis. Chem Res Toxicol. 2007 Jul;20(7):1038-45.
• [12] Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J Med Chem. 2005 Nov 17;48(23):7282-9.
• [13] Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9.
• [14] 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.
• [15] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032111)
• [16] The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
• [17] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination. Mol Endocrinol. 2009 Jan;23(1):74-85.
• [22] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [23] Benzothiophene selective estrogen receptor modulators with modulated oxidative activity and receptor affinity. J Med Chem. 2007 May 31;50(11):2682-92.
• [24] Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient female mice. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15133-6.
• [25] MF101, a selective estrogen receptor beta modulator for the treatment of menopausal hot flushes: a phase II clinical trial. Menopause. 2009 May-Jun;16(3):458-65.
• [26] Company report (Axcentua)
• [27] S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr. 2005 May;81(5):1072-9.
• [28] Erb-041, an estrogen receptor-beta agonist, inhibits skin photocarcinogenesis in SKH-1 hairless mice by downregulating the WNT signaling pathway. Cancer Prev Res (Phila). 2014 Feb;7(2):186-98.
• [29] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031986)
• [30] Update on alternative therapies for vulvovaginal atrophy. Patient Prefer Adherence. 2011; 5: 533-536.
• [31] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [32] Role of hydrophobic interactions in binding S-(N-aryl/alkyl-N-hydroxycarbamoyl)glutathiones to the active site of the antitumor target enzyme glyoxalase I. J Med Chem. 2000 Oct 19;43(21):3981-6.
• [33] 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.
• [34] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [35] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [36] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [37] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [38] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [39] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [40] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.