Details of the Drug Combination

General Information of Drug Combination (ID: DCH3KF4)

Drug Combination Name

Cantharidin Ciclopirox

Indication

Disease Entry	Status	REF
Diffuse intrinsic pontine glioma	Investigative	[1]

Component Drugs

Cantharidin DMBP5N3

Ciclopirox DMN5T2A

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: SU-DIPG-XIII

Zero Interaction Potency (ZIP) Score: 10.103

Bliss Independence Score: 18.288

Loewe Additivity Score: 0.612

LHighest Single Agent (HSA) Score: 0.664

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Cantharidin

Disease Entry	ICD 11	Status	REF
Molluscum contagiosum infection	1E76	Approved	[2]

Cantharidin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine PP1-alpha (PPP1CA)	TTFLH0E	PP1A_HUMAN	Inhibitor	[6]
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Cantharidin Interacts with 45 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Expression	[7]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Increases Expression	[7]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Increases Expression	[5]
Cocaine esterase (CES2)	OTC647SQ	EST2_HUMAN	Decreases Expression	[8]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[5]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[9]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[5]
Sphingosine 1-phosphate receptor 2 (S1PR2)	OTRTJF29	S1PR2_HUMAN	Increases Expression	[8]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)	OTVT4YA1	ATG7_HUMAN	Increases Expression	[10]
Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)	OTM0GDTP	IF2A_HUMAN	Increases Expression	[10]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[5]
Calpain-1 catalytic subunit (CAPN1)	OTK6OQZR	CAN1_HUMAN	Increases Expression	[5]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[11]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[5]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[9]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[5]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[11]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[11]
Calpain-2 catalytic subunit (CAPN2)	OTIAPE5J	CAN2_HUMAN	Increases Expression	[5]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)	OTRFV19J	ATF4_HUMAN	Increases Expression	[10]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Increases Cleavage	[5]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Affects Expression	[8]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[8]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[5]
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)	OT5BZ1J9	P85A_HUMAN	Decreases Expression	[11]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[5]
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Affects Expression	[8]
Nitric oxide synthase 1 (NOS1)	OT7M8XVG	NOS1_HUMAN	Decreases Expression	[8]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[5]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[5]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Decreases Expression	[11]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[12]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Affects Expression	[11]
Caspase-4 (CASP4)	OTVQTV1L	CASP4_HUMAN	Increases Expression	[5]
Tumor necrosis factor ligand superfamily member 10 (TNFSF10)	OT4PXBTA	TNF10_HUMAN	Increases Expression	[5]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[5]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[11]
Hepcidin (HAMP)	OT607RBL	HEPC_HUMAN	Decreases Expression	[13]
Cyclin-dependent kinase 6 (CDK6)	OTR95N0X	CDK6_HUMAN	Decreases Expression	[5]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Decreases Expression	[11]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[9]
Endonuclease G, mitochondrial (ENDOG)	OT5IM7B3	NUCG_HUMAN	Increases Expression	[5]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[10]
Ubiquitin-like-conjugating enzyme ATG3 (ATG3)	OT28VBVK	ATG3_HUMAN	Increases Expression	[10]
Eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)	OT0DZGY4	E2AK3_HUMAN	Increases Expression	[10]
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⏷ Show the Full List of 45 DOT(s)

Indication(s) of Ciclopirox

Disease Entry	ICD 11	Status	REF
Cutaneous candidiasis	1F23.14	Approved	[3]
Fungal infection	1F29-1F2F	Approved	[4]
Mycoses	1F2Z	Approved	[3]
Onychomycosis	EE12.1	Approved	[3]
Pityriasis simplex	N.A.	Approved	[3]
Tinea corporis	1F28.Y	Approved	[3]
Tinea cruris	1F28.3	Approved	[3]
Tinea versicolor	1F2D.0	Approved	[3]
Tinea pedis	1F28.2	Investigative	[3]

Ciclopirox Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HIF-prolyl hydroxylase (HPH)	TTJQFBG	NOUNIPROTAC	Modulator	[14]
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Ciclopirox Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[15]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Decreases Activity	[16]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[17]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Degradation	[18]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[19]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Stability	[20]
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⏷ Show the Full List of 6 DOT(s)

References

1	Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	Ciclopirox FDA Label
4	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076435.
5	Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo. Environ Toxicol. 2017 Mar;32(3):723-738. doi: 10.1002/tox.22273. Epub 2016 Apr 25.
6	Serine-threonine protein phosphatase inhibitors: development of potential therapeutic strategies. J Med Chem. 2002 Mar 14;45(6):1151-75.
7	Flavonoids as aryl hydrocarbon receptor agonists/antagonists: effects of structure and cell context. Environ Health Perspect. 2003 Dec;111(16):1877-82.
8	Hepatoxicity mechanism of cantharidin-induced liver LO2 cells by LC-MS metabolomics combined traditional approaches. Toxicol Lett. 2020 Oct 15;333:49-61. doi: 10.1016/j.toxlet.2020.07.024. Epub 2020 Jul 26.
9	[Apoptosis induced by cantharidin in human pulmonary carcinoma cells A549 and its molecular mechanisms]. Zhonghua Zhong Liu Za Zhi. 2005 Jun;27(6):330-4.
10	Endoplasmic reticulum stress contributes to autophagy and apoptosis in cantharidin-induced nephrotoxicity. Food Chem Toxicol. 2022 May;163:112986. doi: 10.1016/j.fct.2022.112986. Epub 2022 Apr 6.
11	Cantharidin suppresses gastric cancer cell migration/invasion by inhibiting the PI3K/Akt signaling pathway via CCAT1. Chem Biol Interact. 2020 Feb 1;317:108939. doi: 10.1016/j.cbi.2020.108939. Epub 2020 Jan 13.
12	Analysis of cantharidin-induced nephrotoxicity in HK-2 cells using untargeted metabolomics and an integrative network pharmacology analysis. Food Chem Toxicol. 2020 Dec;146:111845. doi: 10.1016/j.fct.2020.111845. Epub 2020 Nov 2.
13	A HAMP promoter bioassay system for identifying chemical compounds that modulate hepcidin expression. Exp Hematol. 2015 May;43(5):404-413.e5. doi: 10.1016/j.exphem.2015.01.005. Epub 2015 Jan 26.
14	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
15	Chelation of intracellular iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and myeloma cells. Blood. 2009 Oct 1;114(14):3064-73. doi: 10.1182/blood-2009-03-209965. Epub 2009 Jul 9.
16	Discovery of selective glucocorticoid receptor modulators by multiplexed reporter screening. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4929-34. doi: 10.1073/pnas.0812308106. Epub 2009 Mar 2.
17	Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
18	Non-hypoxic stabilization of hypoxia-inducible factor alpha (HIF-alpha): relevance in neural progenitor/stem cells. Neurotox Res. 2009 May;15(4):367-80. doi: 10.1007/s12640-009-9043-z. Epub 2009 Mar 20.
19	Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.
20	Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation. Blood. 2005 Jun 15;105(12):4613-9. doi: 10.1182/blood-2004-10-3980. Epub 2005 Mar 1.