Details of the Drug Combination

General Information of Drug Combination (ID: DCNDMPI)

• Drug Combination Name: Tolnaftate + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Tolnaftate (DM28MU7): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 24.1
  Bliss Independence Score: 24.02
  Loewe Additivity Score: 6.36
  LHighest Single Agent (HSA) Score: 6.49

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tolnaftate

Disease Entry	ICD 11	Status	REF
Dermatophytosis	1F28.2	Approved	[2]
Jock itch	1F28.3	Approved	[2]
Tinea corporis	1F28.Y	Approved	[3]
Tinea cruris	1F28.3	Approved	[3]
Tinea manuum	N.A.	Approved	[4]
Tinea versicolor	1F2D.0	Approved	[5]
Tinea pedis	1F28.2	Investigative	[6]

Tolnaftate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Squalene monooxygenase (SQLE)	TTE14XG	ERG1_HUMAN	Inhibitor	[13]

Tolnaftate Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[14]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[14]

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[7]
High-risk myelofibrosis	2A20.2	Approved	[8]
Myelofibrosis	2A22	Approved	[9]
Myeloproliferative neoplasm	2A20	Approved	[10]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[11]
Pancreatic cancer	2C10	Phase 3	[8]
Atopic dermatitis	EA80	Phase 1/2	[12]
Vitiligo	ED63.0	Phase 1/2	[12]

Ruxolitinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[15]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[15]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[16]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[17]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[17]

Ruxolitinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Increases ADR	[18]

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] Drug information of Tolnaftate, 2008. eduDrugs.
• [3] Butenafine. Drugs. 1998 Mar;55(3):405-12; discussion 413.
• [4] A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
• [5] Oxiconazole nitrate: pharmacology, efficacy, and safety of a new imidazole antifungal agent. Clin Ther. 1991 Jan-Feb;13(1):126-41.
• [6] Tinea pedis: an updated review. Drugs Context. 2023 Jun 29;12:2023-5-1.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] 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. (Ligand id: 5688).
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] Ruxolitinib FDA Label
• [11] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] Effects of squalene epoxidase inhibitors on Candida albicans. Antimicrob Agents Chemother. 1992 Aug;36(8):1779-81.
• [14] Anti-mycotics suppress interleukin-4 and interleukin-5 production in anti-CD3 plus anti-CD28-stimulated T cells from patients with atopic dermatitis. J Invest Dermatol. 2001 Dec;117(6):1635-46. doi: 10.1046/j.0022-202x.2001.01566.x.
• [15] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [16] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [17] The Use of Anti-Inflammatory Drugs in the Treatment of People With Severe Coronavirus Disease 2019 (COVID-19): The Perspectives of Clinical Immunologists From China. Clin Immunol. 2020 May;214:108393.
• [18] 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.