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

General Information of Drug (ID: DM96ECL)

• Drug Name: CHRYSOERIOL Drug Info
• Synonyms: Chrysoeriol; 491-71-4; Chryseriol; Luteolin 3'-methyl ether; 3'-O-Methylluteolin; 3'-O-Methyluteolin; 5,7-Dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-4-benzopyrone; 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-4H-chromen-4-one; 5,7-Dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-4H-1-benzopyran-4-one; 4H-1-Benzopyran-4-one, 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-; UNII-Q813145M20; EINECS 207-742-6; BRN 0295004; CHEMBL214321; CHEBI:16514

Indication

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

• Cross-matching ID:
  PubChem CID: 5280666
  ChEBI ID: CHEBI:16514
  CAS Number: CAS 491-71-4
  TTD Drug ID: DM96ECL

Molecule-Related Drug Atlas

Drug(s) Targeting Xanthine dehydrogenase/oxidase (XDH)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Allopurinol	DMLPAOB	Gout	FA25	Approved	[5]
Febuxostat	DMDEXQ0	Hyperuricaemia	5C55.Y	Approved	[6]
Fosdenopterin	DMR0TYK	Molybdenum cofactor deficiency	5B5K.A	Approved	[7]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[8]
Oxypurinol	DMURH4X	Heart failure	BD10-BD13	Phase 2/3	[9]
BAICALEIN	DM4C7E6	Influenza virus infection	1E30-1E32	Phase 2	[2]
Topiroxostat	DMA04DE	Gout	FA25	Phase 2	[10]
TMX-049	DME8PFQ	Diabetic nephropathy	GB61.Z	Phase 2	[11]
LC-350189	DMHT3CB	Gout	FA25	Phase 1	[12]
Azaindole derivative 5	DMD2BL3	N. A.	N. A.	Patented	[13]

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	[1]
NARINGENIN	DMHAZLM	N. A.	N. A.	Phase 1	[1]
Chrysin	DM7V2LG	Discovery agent	N.A.	Investigative	[1]
APIGENIN	DMI3491	Discovery agent	N.A.	Investigative	[1]
KAEMPFEROL	DMHEMUB	Discovery agent	N.A.	Investigative	[1]
ISORHAMNETIN	DMQ4Z6E	Discovery agent	N.A.	Investigative	[1]
ACACETIN	DMQOB0X	Discovery agent	N.A.	Investigative	[1]
TRISMETHOXYRESVERATROL	DM6USPC	Discovery agent	N.A.	Investigative	[14]
Galangin	DM5TQ2O	Discovery agent	N.A.	Investigative	[1]
DIOSMETIN	DM4KXIM	Discovery agent	N.A.	Investigative	[1]

Drug(s) Affected By Multidrug resistance-associated protein 1 (ABCC1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[15]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[16]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[19]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[20]
Epirubicin	DMPDW6T	Solid tumour/cancer	2A00-2F9Z	Approved	[21]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[22]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[23]
Dactinomycin	DM2YGNW	Adult kidney Wilms tumor		Approved	[23]

Drug(s) Affected By Melatonin receptor type 1A (MTNR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[3]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[24]
Agomelatine	DMXYA5K	Major depressive disorder	6A70.3	Withdrawn from market	[25]
4P-PDOT	DMEMN0W	Discovery agent	N.A.	Investigative	[26]

Drug(s) Affected By Melatonin receptor type 1B (MTNR1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[27]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[28]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[29]
Melatonin	DMKWFBT	Depression	6A70-6A7Z	Approved	[30]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[31]
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[3]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[24]
Agomelatine	DMXYA5K	Major depressive disorder	6A70.3	Withdrawn from market	[25]
4P-PDOT	DMEMN0W	Discovery agent	N.A.	Investigative	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cytochrome P450 1B1 (CYP1B1)	TTI84H7	CP1B1_HUMAN	Inhibitor	[1]
Xanthine dehydrogenase/oxidase (XDH)	TT7RJY8	XDH_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Melatonin receptor type 1A (MTNR1A)	OTYYV8JK	MTR1A_HUMAN	Protein Interaction/Cellular Processes	[3]
Melatonin receptor type 1B (MTNR1B)	OT6VFHX9	MTR1B_HUMAN	Protein Interaction/Cellular Processes	[3]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Gene/Protein Processing	[4]

References

• [1] Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
• [2] Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
• [3] Old and new inhibitors of quinone reductase 2. Chem Biol Interact. 2010 Jul 30;186(2):103-9. doi: 10.1016/j.cbi.2010.04.006. Epub 2010 May 4.
• [4] Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2. Biochem Pharmacol. 2005 Feb 15;69(4):699-708. doi: 10.1016/j.bcp.2004.11.002. Epub 2004 Dec 23.
• [5] Allopurinol: xanthine oxidase inhibitor. Tex Med. 1966 Jan;62(1):100-1.
• [6] Clinical pipeline report, company report or official report of Takeda (2009).
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [8] Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod. 2009 Apr;72(4):725-31.
• [9] Oxypurinol as an inhibitor of xanthine oxidase-catalyzed production of superoxide radical. Biochem Pharmacol. 1988 Jan 15;37(2):349-52.
• [10] QT/QTc study conducted in Japanese adult healthy subjects: a novel xanthine oxidase inhibitor topiroxostat was not associated with QT prolongation. J Clin Pharmacol. 2014 Apr;54(4):446-52.
• [11] Clinical pipeline report, company report or official report of Teijin Pharma.
• [12] Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. Drug Des Devel Ther. 2015 Aug 31;9:5033-49.
• [13] An updated patent review: xanthine oxidase inhibitors for the treatment of hyperuricemia and gout (2011-2015).Expert Opin Ther Pat. 2017 Mar;27(3):311-345.
• [14] 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.
• [15] Characterization of multidrug transporter-mediated efflux of avermectins in human and mouse neuroblastoma cell lines. Toxicol Lett. 2015 Jun 15;235(3):189-98. doi: 10.1016/j.toxlet.2015.04.005. Epub 2015 Apr 9.
• [16] Folate concentration dependent transport activity of the Multidrug Resistance Protein 1 (ABCC1). Biochem Pharmacol. 2004 Apr 15;67(8):1541-8.
• [17] Methotrexate normalizes up-regulated folate pathway genes in rheumatoid arthritis. Arthritis Rheum. 2013 Nov;65(11):2791-802.
• [18] Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression. Toxicology. 2002 Feb 28;171(2-3):137-46.
• [19] Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
• [20] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [21] Co-encapsulation of chrysophsin-1 and epirubicin in PEGylated liposomes circumvents multidrug resistance in HeLa cells. Chem Biol Interact. 2015 Dec 5;242:13-23. doi: 10.1016/j.cbi.2015.08.023. Epub 2015 Sep 1.
• [22] Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance. Hematology. 2007 Dec;12(6):511-7. doi: 10.1080/10245330701562535.
• [23] Functional analysis of MRP1 cloned from bovine. FEBS Lett. 2002 Jun 19;521(1-3):211-3. doi: 10.1016/s0014-5793(02)02816-8.
• [24] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [25] Synthesis of phenalene and acenaphthene derivatives as new conformationally restricted ligands for melatonin receptors. J Med Chem. 2000 Nov 2;43(22):4051-62. doi: 10.1021/jm000922c.
• [26] Toward the definition of stereochemical requirements for MT2-selective antagonists and partial agonists by studying 4-phenyl-2-propionamidotetralin derivatives. J Med Chem. 2011 Dec 22;54(24):8362-72. doi: 10.1021/jm200790v. Epub 2011 Nov 18.
• [27] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [28] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [29] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [30] Melatonin antagonizes apoptosis via receptor interaction in U937 monocytic cells. J Pineal Res. 2007 Sep;43(2):154-62. doi: 10.1111/j.1600-079X.2007.00455.x.
• [31] Common genetic variation in MTNR1B is associated with serum testosterone, glucose tolerance, and insulin secretion in polycystic ovary syndrome patients. Fertil Steril. 2010 Nov;94(6):2486-9, 2489.e1-2. doi: 10.1016/j.fertnstert.2010.01.059. Epub 2010 Mar 6.