Details of the Drug Combination

General Information of Drug Combination (ID: DCKFK9F)

• Drug Combination Name: Parthenolide + Ciclopirox
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Parthenolide (DMCQBFT): Small molecular drug
  Ciclopirox (DMN5T2A): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 20.206
  Bliss Independence Score: 24.787
  Loewe Additivity Score: 0.746
  LHighest Single Agent (HSA) Score: 5.083

Molecular Interaction Atlas of This Drug Combination

Parthenolide Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	TTJ3E9X	IKKB_HUMAN	Inhibitor	[4]
Nuclear factor NF-kappa-B (NFKB)	TTSXVID	NFKB1_HUMAN; NFKB2_HUMAN; TF65_HUMAN; RELB_HUMAN; REL_HUMAN	Inhibitor	[5]

Indication(s) of Ciclopirox

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

Ciclopirox Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HIF-prolyl hydroxylase (HPH)	TTJQFBG	NOUNIPROTAC	Modulator	[6]

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	[7]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Decreases Activity	[8]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[9]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Degradation	[10]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[11]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Stability	[12]

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] Ciclopirox FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076435.
• [4] The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001 Aug;8(8):759-66.
• [5] Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med. 2005 Jan 3;201(1):105-15.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.