Details of the Drug Combination

General Information of Drug Combination (ID: DCS5CFG)

Drug Combination Name

GDC-0980/RG7422 Ciclopirox

Indication

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

Component Drugs

GDC-0980/RG7422 DMF3MV1

Ciclopirox DMN5T2A

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: SU-DIPG-XIII

Zero Interaction Potency (ZIP) Score: 12.185

Bliss Independence Score: 14.046

Loewe Additivity Score: 4.347

LHighest Single Agent (HSA) Score: 7.849

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of GDC-0980/RG7422

Disease Entry	ICD 11	Status	REF
Non-hodgkin lymphoma	2B33.5	Phase 2	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

GDC-0980/RG7422 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Modulator	[7]
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[8]
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GDC-0980/RG7422 Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD)	OTOMP6TH	PK3CD_HUMAN	Decreases Activity	[8]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[8]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[8]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[8]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[8]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB)	OTO8JQJA	PK3CB_HUMAN	Decreases Activity	[8]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PIK3CG)	OT3FAU4Y	PK3CG_HUMAN	Decreases Activity	[8]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[6]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Increases Expression	[6]
Tuberin (TSC2)	OT47LWI9	TSC2_HUMAN	Decreases Phosphorylation	[9]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[6]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Decreases Phosphorylation	[9]
Cyclin-G2 (CCNG2)	OTII38K2	CCNG2_HUMAN	Increases Expression	[6]
Atos homolog protein A (ATOSA)	OTWFM5G0	ATOSA_HUMAN	Increases Expression	[6]
Phosphoinositide-3-kinase-interacting protein 1 (PIK3IP1)	OTWE5G4T	P3IP1_HUMAN	Increases Expression	[6]
Serine/threonine-protein kinase STK11 (STK11)	OT1YZSP3	STK11_HUMAN	Increases Response To Substance	[6]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Response To Substance	[6]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Response To Substance	[6]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)	OTTOMI8J	PK3CA_HUMAN	Increases Response To Substance	[6]
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⏷ Show the Full List of 19 DOT(s)

Indication(s) of Ciclopirox

Disease Entry	ICD 11	Status	REF
Cutaneous candidiasis	1F23.14	Approved	[4]
Fungal infection	1F29-1F2F	Approved	[5]
Mycoses	1F2Z	Approved	[4]
Onychomycosis	EE12.1	Approved	[4]
Pityriasis simplex	N.A.	Approved	[4]
Tinea corporis	1F28.Y	Approved	[4]
Tinea cruris	1F28.3	Approved	[4]
Tinea versicolor	1F2D.0	Approved	[4]
Tinea pedis	1F28.2	Investigative	[4]

Ciclopirox Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HIF-prolyl hydroxylase (HPH)	TTJQFBG	NOUNIPROTAC	Modulator	[10]
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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	[11]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Decreases Activity	[12]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[13]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Degradation	[14]
Microtubule-associated protein tau (MAPT)	OTMTP2Z7	TAU_HUMAN	Decreases Expression	[15]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Stability	[16]
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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	Clinical pipeline report, company report or official report of Roche.
3	Clinical pipeline report, company report or official report of Genentech (2011).
4	Ciclopirox FDA Label
5	FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 076435.
6	Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models. Clin Cancer Res. 2012 Dec 15;18(24):6771-83. doi: 10.1158/1078-0432.CCR-12-2347. Epub 2012 Nov 7.
7	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2109).
8	GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36.
9	Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells. Mol Cancer Ther. 2012 Jul;11(7):1510-7. doi: 10.1158/1535-7163.MCT-11-0907. Epub 2012 Apr 24.
10	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
11	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.
12	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.
13	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.
14	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.
15	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.
16	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.