Details of the Drug Combination

General Information of Drug Combination (ID: DCQ8895)

• Drug Combination Name: Sumatriptan + Enalaprilat
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Sumatriptan (DMVYXR8): Small molecular drug
  Enalaprilat (DMFYAM1): N.A.
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 5.88
  Bliss Independence Score: 5.88
  Loewe Additivity Score: 18.73
  LHighest Single Agent (HSA) Score: 18.74

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sumatriptan

Disease Entry	ICD 11	Status	REF
Cluster headache	8A81.0	Approved	[2]
Migraine	8A80	Approved	[3]
Migraine disorder	N.A.	Approved	[2]

Sumatriptan Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Agonist	[6]

Sumatriptan Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[8]

Sumatriptan Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Decreases Expression	[9]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Decreases Expression	[10]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)	OTA6HYBA	GBB3_HUMAN	Increases Response	[11]
5-hydroxytryptamine receptor 1F (HTR1F)	OTALAXPA	5HT1F_HUMAN	Increases ADR	[12]
Calcitonin gene-related peptide 1 (CALCA)	OTQSXM9Z	CALCA_HUMAN	Increases ADR	[12]

Indication(s) of Enalaprilat

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[4]
Hypertension	BA00-BA04	Approved	[5]
Malignant essential hypertension	BA00	Approved	[4]

Enalaprilat Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensin-converting enzyme (ACE)	TTL69WB	ACE_HUMAN	Inhibitor	[13]

Enalaprilat Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[14]

Enalaprilat Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Dipeptidase (pepV)	DEQMBHW	Q84BU9_LACLH	Metabolism	[15]

Enalaprilat Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Secretion	[16]
B1 bradykinin receptor (BDKRB1)	OT1DHSVQ	BKRB1_HUMAN	Increases Activity	[17]
Organic anion transporter 3 (SLC22A8)	OT8BY933	S22A8_HUMAN	Increases Uptake	[18]
Solute carrier family 22 member 11 (SLC22A11)	OTAJLNJZ	S22AB_HUMAN	Increases Uptake	[18]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Affects Abundance	[19]

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] Sumatriptan FDA Label
• [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: 54).
• [4] Enalaprilat FDA Label
• [5] 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: 6332).
• [6] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [7] HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption: role of the mucus layer. J Pharm Sci. 2001 Oct;90(10):1608-19. Comparative Study
• [8] 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.
• [9] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
• [10] The effects of oral sumatriptan, a 5-HT1 receptor agonist, on circulating ACTH and cortisol concentrations in man. Br J Clin Pharmacol. 1995 Apr;39(4):389-95. doi: 10.1111/j.1365-2125.1995.tb04467.x.
• [11] G protein beta3 polymorphism and triptan response in cluster headache. Clin Pharmacol Ther. 2007 Oct;82(4):396-401. doi: 10.1038/sj.clpt.6100159. Epub 2007 Mar 14.
• [12] 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.
• [13] Analysis of Vancomycin in the Hindlimb Vascular Bed of the Rat. Am J Ther. 1996 Oct;3(10):681-687.
• [14] Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74.
• [15] Characterization and kinetic analysis of enzyme-substrate recognition by three recombinant lactococcal PepVs. Arch Biochem Biophys. 2006 Oct 15;454(2):137-45.
• [16] Different effects of angiotensin converting enzyme inhibitors on endothelin-1 and nitric oxide balance in human vascular endothelial cells: evidence of an oxidant-sensitive pathway. Mediators Inflamm. 2008;2008:305087. doi: 10.1155/2008/305087. Epub 2008 Dec 1.
• [17] Novel mode of action of angiotensin I converting enzyme inhibitors: direct activation of bradykinin B1 receptor. J Biol Chem. 2002 May 10;277(19):16847-52. doi: 10.1074/jbc.M200355200. Epub 2002 Mar 5.
• [18] Completing the Enalaprilat Excretion Pathway-Renal Handling by the Proximal Tubule. Pharmaceutics. 2020 Sep 30;12(10):935. doi: 10.3390/pharmaceutics12100935.
• [19] Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther. 2011 May;33(5):655-63. doi: 10.1016/j.clinthera.2011.04.018.