Details of the Drug Combination

General Information of Drug Combination (ID: DCGZRKA)

• Drug Combination Name: Febuxostat + M102
• Indication: Hyperuricemia; Status: Phase 2 [1]
• Component Drugs:
  Febuxostat (DMDEXQ0): Small molecular drug
  M102 (DMUFIO9): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Febuxostat

Disease Entry	ICD 11	Status	REF
Hyperuricaemia	5C55.Y	Approved	[2]

Febuxostat Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Xanthine dehydrogenase/oxidase (XDH)	TT7RJY8	XDH_HUMAN	Inhibitor	[5]

Febuxostat Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[6]

Febuxostat Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Ras-related protein M-Ras (MRAS)	OTNCVCQW	RASM_HUMAN	Increases Expression	[4]
Growth arrest and DNA damage-inducible protein GADD45 gamma (GADD45G)	OT8V1J4M	GA45G_HUMAN	Increases Expression	[4]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[7]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[7]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1)	OTGP6GA4	NR4A1_HUMAN	Increases Expression	[4]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Phosphorylation	[4]
Dual specificity protein phosphatase 4 (DUSP4)	OT6WAO12	DUS4_HUMAN	Increases Expression	[4]
Dual specificity protein phosphatase 8 (DUSP8)	OTPLMPG9	DUS8_HUMAN	Increases Expression	[4]
Dual specificity protein phosphatase 5 (DUSP5)	OTH96RA7	DUS5_HUMAN	Increases Expression	[4]
Interleukin-1 receptor accessory protein (IL1RAP)	OTEU321R	IL1AP_HUMAN	Increases Expression	[4]
Dual specificity protein phosphatase 10 (DUSP10)	OTNG467B	DUS10_HUMAN	Increases Expression	[4]

Indication(s) of M102

Disease Entry	ICD 11	Status	REF
Amyotrophic lateral sclerosis	8B60.0	Preclinical	[3]

M102 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nuclear factor erythroid 2-related factor 2 (Nrf2)	TTA6ZN2	NF2L2_HUMAN	Activator	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Gout	DC0WGVW	N. A.	Phase 2	[9]

References

• [1] ClinicalTrials.gov (NCT01416402) Open Label Safety/Efficacy Study of Arhalofenate in Combination With Febuxostat for Hyperuricemia in Gout Patients
• [2] 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: 6817).
• [3] Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov. 2019 Apr;18(4):295-317.
• [4] Febuxostat Increases Ventricular Arrhythmogenesis Through Calcium Handling Dysregulation in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Toxicol Sci. 2022 Sep 24;189(2):216-224. doi: 10.1093/toxsci/kfac073.
• [5] Clinical pipeline report, company report or official report of Takeda (2009).
• [6] In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition. Xenobiotica. 2008 May;38(5):496-510.
• [7] Allopurinol induces innate immune responses through mitogen-activated protein kinase signaling pathways in HL-60 cells. J Appl Toxicol. 2016 Sep;36(9):1120-8. doi: 10.1002/jat.3272. Epub 2015 Dec 7.
• [8] Clinical pipeline report, company report or official report of Aclipse Therapeutics.
• [9] ClinicalTrials.gov (NCT02252835) Evaluate the PK, PD, and Safety of Arhalofenate in Combination With Febuxostat for Hyperuricemia in Patients With Gout