Details of the Drug Combination

General Information of Drug Combination (ID: DCGPRCC)

• Drug Combination Name: RDEA3170 + Febuxostat
• Indication: Asymptomatic Hyperuricemia; Status: Phase 2 [1]
• Component Drugs:
  RDEA3170 (DM1TKG4): N.A.
  Febuxostat (DMDEXQ0): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of RDEA3170

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

RDEA3170 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Urate anion exchanger 1 (URAT1)	TTA592U	S22AC_HUMAN	Modulator	[4]

Indication(s) of Febuxostat

Disease Entry	ICD 11	Status	REF
Hyperuricaemia	5C55.Y	Approved	[3]

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	[6]

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	[7]

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

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Asymptomatic Hyperuricemia	DCWDX6A	N. A.	Phase 2	[1]

References

• [1] ClinicalTrials.gov (NCT03316131) A Study to Assess the Effect of Intensive Uric Acid (UA) Lowering Therapy With RDEA3170, Febuxostat, Dapagliflozin on Urinary Excretion of UA
• [2] ClinicalTrials.gov (NCT02078219) Phase II Dose Finding Study of RDEA3170 Versus Placebo in Japanese Patients With Gout or Asymptomatic Hyperuricemia. U.S. National Institutes of Health.
• [3] 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).
• [4] The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013; 14: 164.
• [5] 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.
• [6] Clinical pipeline report, company report or official report of Takeda (2009).
• [7] 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.
• [8] 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.