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

General Information of Drug (ID: DM6VY3P)

• Drug Name: NSC-94258 Drug Info
• Synonyms: 7-Hydroxyflavone; 6665-86-7; 7-Hydroxy-2-phenyl-4H-chromen-4-one; Flavone, 7-hydroxy-; 7-Hydroxy-2-phenyl-4-benzopyrone; 4H-1-Benzopyran-4-one, 7-hydroxy-2-phenyl-; 7-hydroxy-2-phenylchromen-4-one; 4H-1-Benzopyran-4-one, 7-hydroxy-; 7-Hydroxy-2-phenyl-chromen-4-one; NSC 94258; UNII-ZE72458E4L; EINECS 229-705-3; NSC-94258; MLS002695239; CHEBI:2268; CHEMBL276915; MQGPSCMMNJKMHQ-UHFFFAOYSA-N; ZE72458E4L; NSC94258; MFCD00006835; 7-Hydroxy-2-phenyl-4H-1-benzopyran-4-one; H-5100; SR-01000359106; 7-Hydroxyflavone, 11; 7-Hydroxy-flavone,

Indication

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

• Cross-matching ID:
  PubChem CID: 5281894
  ChEBI ID: CHEBI:2268
  CAS Number: CAS 6665-86-7
  TTD Drug ID: DM6VY3P

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	[4]
Letrozole	DMH07Y3	Hormonally-responsive breast cancer	2C60-2C65	Approved	[5]
Exemestane	DM9HPW3	Hormonally-responsive breast cancer	2C60-2C65	Approved	[5]
Aminoglutethimide	DMWFHMZ	Cushing disease	5A70	Approved	[6]
FADROZOLE	DM3C5GZ	Breast cancer	2C60-2C65	Approved	[7]
Testolactone	DMVY4GN	Breast cancer	2C60-2C65	Approved	[8]
Atamestane + Toremifene	DM3QLK2	Breast cancer	2C60-2C65	Phase 3	[9]
LIAROZOLE	DM4OYXE	Dermatological disease	DA24.Y	Phase 2/3	[3]
Coumate	DMVKW0N	Breast cancer	2C60-2C65	Phase 2	[10]
Dextromethorphan+quinidine	DMFI5J4	Diabetic neuropathy	8C0Z	Phase 2	[11]

Drug(s) Targeting Aldose reductase (AKR1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epalrestat	DM5OGK0	Diabetic neuropathy	8C0Z	Approved	[12]
Sulindac	DM2QHZU	Rheumatoid arthritis	FA20	Approved	[13]
Fidarestat	DMZL1I8	Diabetic complication	5A2Y	Phase 3	[14]
Ranirestat	DMD5QRS	Diabetic neuropathy	8C0Z	Phase 3	[15]
Contigoside B	DMX9V8K	Thrombosis	DB61-GB90	Phase 2/3	[16]
BNV-222	DMYFQJL	Diabetic neuropathy	8C0Z	Phase 2/3	[17]
LIDORESTAT	DMA0RI9	Diabetic complication	5A2Y	Phase 2	[18]
QR-333	DMKVIWM	Diabetic neuropathy	8C0Z	Phase 2	[19]
ADMVA	DM819CO	Diabetic complication	5A2Y	Phase 2	[15]
M-16209	DMZ7YX3	Diabetic complication	5A2Y	Phase 2	[20]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Naringenin	DMHAZLM	N. A.	N. A.	Phase 1	[1]
Nicotinamide-Adenine-Dinucleotide	DM9LRKB	N. A.	N. A.	Investigative	[21]
2'-Monophosphoadenosine 5'-Diphosphoribose	DME9S8M	Discovery agent	N.A.	Investigative	[21]
Apigenin	DMI3491	Discovery agent	N.A.	Investigative	[1]
Kaempferol	DMHEMUB	Discovery agent	N.A.	Investigative	[1]
4-ANDROSTENE-3-17-DIONE	DMSE8NU	Discovery agent	N.A.	Investigative	[21]
6-(3-Hydroxy-phenyl)-naphthalen-2-ol	DMH8WA2	Discovery agent	N.A.	Investigative	[22]
7-(3-Hydroxy-phenyl)-naphthalen-2-ol	DM2I91C	Discovery agent	N.A.	Investigative	[23]
4-[5-(3-Hydroxyphenyl)-3-thienyl]-2-methylphenol	DM7ERYJ	Discovery agent	N.A.	Investigative	[24]
6-(4-Hydroxy-phenyl)-naphthalen-1-ol	DM2V9XI	Discovery agent	N.A.	Investigative	[23]

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]
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[3]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)	TTIWB6L	DHB1_HUMAN	Inhibitor	[1]

References

• [1] 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.
• [2] 1-Benzopyran-4-one antioxidants as aldose reductase inhibitors. J Med Chem. 1999 Jun 3;42(11):1881-93.
• [3] 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.
• [4] 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.
• [5] Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51.
• [6] Aminoglutethimide-induced protein free radical formation on myeloperoxidase: a potential mechanism of agranulocytosis. Chem Res Toxicol. 2007 Jul;20(7):1038-45.
• [7] Enantioselective nonsteroidal aromatase inhibitors identified through a multidisciplinary medicinal chemistry approach. J Med Chem. 2005 Nov 17;48(23):7282-9.
• [8] Aromatase inhibitors for male infertility. J Urol. 2002 Feb;167(2 Pt 1):624-9.
• [9] 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.
• [10] 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.
• [11] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [12] 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.
• [13] Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.
• [14] 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.
• [15] 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).
• [16] Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes. J Nat Prod. 1996 Apr;59(4):443-5.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [22] 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.
• [23] 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.
• [24] 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.