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

General Information of Drug (ID: DMBUJVX)

• Drug Name: Phenoxodiol Drug Info
• Synonyms: Dehydroequol; Idronoxil; Haginin E; NV 06; NV-06; Idronoxil (USAN/INN); 2H-1-benzopyran-7-0,1,3-(4-hydroxyphenyl); 3-(4-Hydroxyphenyl)-2H-1-benzopyran-7-ol; 3-(4-Hydroxyphenyl)-2H-chromen-7-ol; 7-hydroxy-3-hydroxyphenyl-1H-benzopyran

Indication

Disease Entry	ICD 11	Status	REF
Ovarian cancer	2C73	Phase 1/2	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 219100
  CAS Number: CAS 81267-65-4
  TTD Drug ID: DMBUJVX

Molecule-Related Drug Atlas

Drug(s) Targeting X-linked inhibitor of apoptosis protein (XIAP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT-406	DMVJW0S	Squamous head and neck cell carcinom	2D60.0	Phase 3	[5]
Birinapant	DM6PBUM	Lymphoma	2A80-2A86	Phase 2	[6]
APG-1387	DMLEKUY	Haematological malignancy	2B33.Y	Phase 1	[7]
HGS-1029	DMS9WXG	Haematological malignancy	2B33.Y	Phase 1	[8]
GDC-0152	DM1B3UM	Obesity	5B81	Phase 1	[9]
PMID25980951-Compound-6	DMVSW5N	N. A.	N. A.	Patented	[10]
PMID25980951-Compound-27	DMXAH9F	N. A.	N. A.	Patented	[10]
PMID25980951-Compound-43	DMTJRCS	N. A.	N. A.	Patented	[10]
PMID25980951-Compound-1	DMYPT2H	N. A.	N. A.	Patented	[10]
PMID25980951-Compound-44	DMS5896	N. A.	N. A.	Patented	[10]

Drug(s) Targeting Sphingosine kinase 1 (SPHK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[11]
PMID27539678-Compound-6	DMBKNDE	N. A.	N. A.	Patented	[12]
Methylbenzenesulfonamide derivative 1	DMUNME2	N. A.	N. A.	Patented	[12]
PMID27539678-Compound-12	DMNIKTA	N. A.	N. A.	Patented	[12]
PMID27539678-Compound-10	DM61SR0	N. A.	N. A.	Patented	[12]
PMID27539678-Compound-16	DMMDJH8	N. A.	N. A.	Patented	[12]
PMID27539678-Compound-14	DMZ02LA	N. A.	N. A.	Patented	[12]
PMID27539678-Compound-13	DM1J2V8	N. A.	N. A.	Patented	[12]
PMID27539678-Compound-11	DMIKAJC	N. A.	N. A.	Patented	[12]
PMID27539678-Compound-7	DMQAC4K	N. A.	N. A.	Patented	[12]

Drug(s) Affected By BH3-interacting domain death agonist (BID)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[14]
Selenium	DM25CGV	N. A.	N. A.	Approved	[15]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[16]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[17]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[18]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[20]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[21]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[22]

Drug(s) Affected By Ecto-NOX disulfide-thiol exchanger 2 (ENOX2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[25]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[26]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[27]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[28]
Epigallocatechin gallate	DMCGWBJ	Hepatic fibrosis	DB93.0	Phase 3	[4]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[29]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[30]
Milchsaure	DM462BT	Pruritus	EC90	Investigative	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sphingosine kinase 1 (SPHK1)	TTOHFIY	SPHK1_HUMAN	Modulator	[2]
X-linked inhibitor of apoptosis protein (XIAP)	TTR7B60	XIAP_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
BH3-interacting domain death agonist (BID)	OTOSHSHU	BID_HUMAN	Gene/Protein Processing	[3]
E3 ubiquitin-protein ligase XIAP	OT24GP9B	XIAP_HUMAN	Protein Interaction/Cellular Processes	[3]
Ecto-NOX disulfide-thiol exchanger 2 (ENOX2)	OTMDA97Z	ENOX2_HUMAN	Gene/Protein Processing	[4]

References

• [1] ClinicalTrials.gov (NCT00382811) OVATURE (OVArian TUmor REsponse) A Phase III Study of Weekly Carboplatin With and Without Phenoxodiol in Patients With Platinum-Resistant, Recurrent Epithelial Ovarian Cancer. U.S. National Institutes of Health.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] Molecular mechanism of phenoxodiol-induced apoptosis in ovarian carcinoma cells. Cancer. 2006 Feb 1;106(3):599-608. doi: 10.1002/cncr.21633.
• [4] Reciprocal relationship between cytosolic NADH and ENOX2 inhibition triggers sphingolipid-induced apoptosis in HeLa cells. J Cell Biochem. 2010 Aug 15;110(6):1504-11. doi: 10.1002/jcb.22724.
• [5] Debio 1143, an antagonist of multiple inhibitor-of-apoptosis proteins, activates apoptosis and enhances radiosensitization of non-small cell lung c... Am J Cancer Res. 2014 Nov 19;4(6):943-51.
• [6] cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1- and RIPK3-dependent manner. Blood. 2014 Apr 17;123(16):2562-72.
• [7] XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells.Theranostics. 2018 Feb 5;8(6):1494-1510.
• [8] Clinical pipeline report, company report or official report of Aegera Therapeutics Inc.
• [9] Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem. 2012 May 10;55(9):4101-13.
• [10] Small molecule inhibitor of apoptosis proteins antagonists: a patent review.Expert Opin Ther Pat. 2015 Jul;25(7):755-74.
• [11] Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma.Oncotarget. 2016 Dec 6;7(49):80586-80598.
• [12] Sphingosine kinase inhibitors: a review of patent literature (2006-2015).Expert Opin Ther Pat. 2016 Dec;26(12):1409-1416.
• [13] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [14] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [15] Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells. Cancer Biol Ther. 2002 May-Jun;1(3):287-90. doi: 10.4161/cbt.83.
• [16] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [17] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [18] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [19] Combination of Poly I:C and arsenic trioxide triggers apoptosis synergistically via activation of TLR3 and mitochondrial pathways in hepatocellular carcinoma cells. Cell Biol Int. 2011 Aug;35(8):803-10. doi: 10.1042/CBI20100739.
• [20] Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2005 Oct;289(4):G731-8. doi: 10.1152/ajpgi.00150.2005. Epub 2005 Jun 23.
• [21] p38 MAPK/PP2Ac/TTP pathway on the connection of TNF- and caspases activation on hydroquinone-induced apoptosis. Carcinogenesis. 2013 Apr;34(4):818-27. doi: 10.1093/carcin/bgs409. Epub 2013 Jan 3.
• [22] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [23] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [24] 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.
• [25] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [26] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [27] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [28] tNOX is both necessary and sufficient as a cellular target for the anticancer actions of capsaicin and the green tea catechin (-)-epigallocatechin-3-gallate. Biofactors. 2004;20(4):235-49.
• [29] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [30] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [31] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.