Details of the Drug Combination

General Information of Drug Combination (ID: DCGUA00)

• Drug Combination Name: Sumatriptan + Acitretin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Sumatriptan (DMVYXR8): Small molecular drug
  Acitretin (DM8BKU9): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 7.12
  Bliss Independence Score: 7.12
  Loewe Additivity Score: 16.98
  LHighest Single Agent (HSA) Score: 16.99

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	[5]

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	[6]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]

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	[8]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Decreases Expression	[9]
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3)	OTA6HYBA	GBB3_HUMAN	Increases Response	[10]
5-hydroxytryptamine receptor 1F (HTR1F)	OTALAXPA	5HT1F_HUMAN	Increases ADR	[11]
Calcitonin gene-related peptide 1 (CALCA)	OTQSXM9Z	CALCA_HUMAN	Increases ADR	[11]

Indication(s) of Acitretin

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Approved	[4]

Acitretin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Signal transducer and activator of transcription 3 (STAT3)	TTH8FZW	STAT3_HUMAN	Inhibitor	[12]

Acitretin Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[13]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Activity	[14]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[15]
Retinoic acid receptor RXR-alpha (RXRA)	OTP1TBDM	RXRA_HUMAN	Affects Binding	[16]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[17]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[14]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Expression	[17]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Expression	[17]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[18]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[14]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[14]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[15]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Increases Expression	[14]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[14]

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] 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: 7598).
• [5] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [6] 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
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2006 Jan;28(1):21-4.
• [13] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [14] Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1. J Cell Mol Med. 2009 Sep;13(9A):2888-98. doi: 10.1111/j.1582-4934.2008.00397.x. Epub 2009 Jun 20.
• [15] [Effects of all-trans-retinoic acid, acitretin and tazarotene on apoptosis and Bax/Bcl-2 expressions of human melanoma cells A375 and the significance]. Di Yi Jun Yi Da Xue Xue Bao. 2005 Aug;25(8):972-4, 978.
• [16] Limited Chemical Structural Diversity Found to Modulate Thyroid Hormone Receptor in the Tox21 Chemical Library. Environ Health Perspect. 2019 Sep;127(9):97009. doi: 10.1289/EHP5314. Epub 2019 Sep 30.
• [17] [Acitretin induces apoptosis and changes of relative signaling pathway in epidermoid carcinoma cell line A431]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Mar;35(2):182-8. doi: 10.3785/j.issn.1008-9292.2006.02.013.
• [18] Effects of ATRA, acitretin and tazarotene on growth and apoptosis of Tca8113 cells. J Huazhong Univ Sci Technolog Med Sci. 2005;25(4):393-6. doi: 10.1007/BF02828205.