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

General Information of Drug (ID: DMU6NBO)

Drug Name

APX3330 Drug Info

Synonyms

E3330; 136164-66-4; E-3330; E 3330; CHEMBL578390; UNII-11267UI968; 11267UI968; (2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]undecanoic acid; (E)-2-((4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylene)undecanoic acid; (2E)-3-(5-(2,3-Dimethoxy-6-methyl-1,4-benzoquinoyl))-2-nonyl-2-propenoic acid; SCHEMBL3758716; SCHEMBL3758719; HMS3886N15; APX 3330; EX-A2212; BDBM50303955; s7445; ZINC14252145; CCG-268389; HY-19357; B5875; CS-0015424; E3330, >=98% (HPLC); A14440; (E)-3-(4,5-dimethoxy-2-methyl-3,6-dioxocyclohexa-1,4-dienyl)-2-nonylpropenoic acid; (E)-3-(5,6-Dimethoxy-3-methyl-14-dioxocyclohexa-25-dienyl)-2-nonylpropenoic Acid; Undecanoic acid, 2-((4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)methylene)-, (E)-

Indication

Disease Entry	ICD 11	Status	REF
Diabetic retinopathy	9B71.0	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

Cross-matching ID

PubChem CID: 6439397
ChEBI ID: CHEMBL578390
CAS Number: CAS 136164-66-4
TTD Drug ID: DMU6NBO

Molecule-Related Drug Atlas

Molecule Type:

DTT

DOT

Drug Status:

Clinical Trial Drug(s)

Investigative Drug(s)

Approved Drug(s)

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Drug(s) Targeting AP endonuclease 1 (APEX1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
APX-3330	DMXIMQT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
5-fluoro-1H-indole-2-carboxylic acid	DM9U1HV	Glioma	2A00.0	Investigative	[7]
1,3-bis(1,3-benzothiazol-2-ylthio)acetone	DMP86R3	Glioma	2A00.0	Investigative	[7]
3-benzofuran-2-yl-2-benzothiazol-2-yl-3-oxo-propanenitrile	DMWLIK1	Glioma	2A00.0	Investigative	[7]
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Drug(s) Affected By Baculoviral IAP repeat-containing protein 5 (BIRC5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[8]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[9]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[10]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[11]
Etretinate	DM2CZFA	Keratosis	ED56	Approved	[12]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[13]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[14]
Lapatinib	DM3BH1Y	Breast cancer	2C60-2C65	Approved	[15]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[16]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[17]
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Drug(s) Affected By Mitogen-activated protein kinase 3 (MAPK3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[23]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[24]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[25]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[26]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[27]
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Drug(s) Affected By Mitogen-activated protein kinase 1 (MAPK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[28]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Carvedilol	DMHTEAO	Chronic heart failure	BD1Z	Approved	[29]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[30]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[31]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[32]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[33]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
AP endonuclease 1 (APEX1)	TTHGL48	APEX1_HUMAN	Inhibitor	[3]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[4]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[5]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[5]

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References

1	ClinicalTrials.gov (NCT04692688) Study of the Safety and Efficacy of APX3330 in Diabetic Retinopathy (ZETA-1). U.S. National Institutes of Health.
2	ClinicalTrials.gov (NCT03375086) A Study of APX3330 in Patients With Advanced Solid Tumors (APX3330). U.S. National Institutes of Health.
3	Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic. NPJ Precis Oncol. 2017;1:19.
4	APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells. Oncotarget. 2017 Dec 13;9(13):10962-10977. doi: 10.18632/oncotarget.23493. eCollection 2018 Feb 16.
5	APE1/Ref-1 prevents oxidative inactivation of ERK for G1-to-S progression following lead acetate exposure. Toxicology. 2013 Mar 8;305:120-9. doi: 10.1016/j.tox.2013.01.010. Epub 2013 Jan 28.
6	Inhibition of APE1/Ref-1 redox activity with APX3330 blocks retinal angiogenesis in vitro and in vivo. Vision Res. 2011 Jan;51(1):93-100.
7	Development and evaluation of human AP endonuclease inhibitors in melanoma and glioma cell lines. Br J Cancer. 2011 Feb 15;104(4):653-63.
8	mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
9	Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells. Toxicol Appl Pharmacol. 2017 Nov 15;335:16-27. doi: 10.1016/j.taap.2017.09.017. Epub 2017 Sep 21.
10	Assessment of the cytotoxic, genotoxic, and apoptotic potential of flurbiprofen in HeLa and HepG2 cell lines. J Biochem Mol Toxicol. 2021 Jun;35(6):1-11. doi: 10.1002/jbt.22770. Epub 2021 Mar 11.
11	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.
12	Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
13	Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
14	Apoptotic induction by simvastatin in human lung cancer A549 cells via Akt signaling dependent down-regulation of survivin. Invest New Drugs. 2011 Oct;29(5):945-52. doi: 10.1007/s10637-010-9450-2. Epub 2010 May 13.
15	Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene. 2005 Sep 15;24(41):6213-21. doi: 10.1038/sj.onc.1208774.
16	Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/beta-catenin signaling pathway. Cancer Invest. 2009 Jul;27(6):604-12. doi: 10.1080/07357900802337191.
17	Troglitazone sensitizes tumor cells to TRAIL-induced apoptosis via down-regulation of FLIP and Survivin. Apoptosis. 2006 Sep;11(9):1503-12. doi: 10.1007/s10495-006-8896-3.
18	Treatment with anticancer agents induces dysregulation of specific Wnt signaling pathways in human ovarian luteinized granulosa cells in vitro. Toxicol Sci. 2013 Nov;136(1):183-92. doi: 10.1093/toxsci/kft175. Epub 2013 Aug 16.
19	Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation. J Cell Biochem. 2007 Dec 1;102(5):1271-80. doi: 10.1002/jcb.21357.
20	Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
21	Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
22	Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer. 2006 Mar 15;118(6):1370-80. doi: 10.1002/ijc.21537.
23	Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis. Toxicol Appl Pharmacol. 2014 Mar 1;275(2):176-81. doi: 10.1016/j.taap.2014.01.005. Epub 2014 Jan 17.
24	Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1. J Pharmacol Exp Ther. 2004 Dec;311(3):1232-40. doi: 10.1124/jpet.104.071332. Epub 2004 Jul 19.
25	Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
26	Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
27	SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.
28	Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicol Mech Methods. 2020 Jul;30(6):407-416. doi: 10.1080/15376516.2020.1747126. Epub 2020 Apr 1.
29	A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
30	The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009 Nov;175(5):2226-34.
31	Modulation of apoptosis in HaCaT keratinocytes via differential regulation of ERK signaling pathway by flavonoids. J Biol Chem. 2005 Sep 9;280(36):31498-507. doi: 10.1074/jbc.M505537200. Epub 2005 Jul 13.
32	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
33	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.