Details of the Drug Combination

General Information of Drug Combination (ID: DC49OO4)

• Drug Combination Name: Buspirone + Triamterene
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Buspirone (DMBS632): Small molecular drug
  Triamterene (DM2HU9I): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 13.56
  Bliss Independence Score: 13.56
  Loewe Additivity Score: 27.61
  LHighest Single Agent (HSA) Score: 27.61

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Buspirone

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Approved	[2]

Buspirone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Agonist	[5]

Buspirone Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[8]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Metabolism	[9]

Buspirone Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[10]

Indication(s) of Triamterene

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[3]
Edema	MG29	Approved	[3]
Hypertension	BA00-BA04	Approved	[3]
High blood pressure	BA00	Investigative	[4]

Triamterene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Amiloride-sensitive sodium channel (ENaC)	TTQM7TE	SCNNA_HUMAN; SCNNB_HUMAN; SCNNG_HUMAN; SCNND_HUMAN	Blocker	[11]

Triamterene Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[12]

Triamterene Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[13]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [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: 36).
• [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: 4329).
• [4] Triamterene FDA Label
• [5] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [6] Effects of cytochrome P450 (CYP) 3A4 inhibitors on the anxiolytic action of tandospirone in rat contextual conditioned fear. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):926-31.
• [7] Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes. Drug Metab Dispos. 2005 Apr;33(4):500-7.
• [8] Drug Interactions Flockhart Table
• [9] The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
• [10] Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment. Psychoneuroendocrinology. 2010 May;35(4):481-9. doi: 10.1016/j.psyneuen.2009.08.012. Epub 2009 Sep 16.
• [11] Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem. 2001;11(4):209-18.
• [12] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [13] Rate-limiting biotransformation of triamterene is mediated by CYP1A2. Int J Clin Pharmacol Ther. 2005 Jul;43(7):327-34.