Details of the Drug Combination

General Information of Drug Combination (ID: DCEGWLN)

Drug Combination Name

Pasireotide Diazoxide

Indication

Disease Entry	Status	REF
Gastro-enteropancreatic Neuroendocrine Tumor	Phase 4	[1]

Component Drugs

Pasireotide DMHM7JS

Diazoxide DML1538

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Pasireotide

Disease Entry	ICD 11	Status	REF
Cushing disease	5A70	Approved	[2]

Pasireotide Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Somatostatin receptor type 3 (SSTR3)	TTJX3UE	SSR3_HUMAN	Inhibitor	[5]
Somatostatin receptor type 1 (SSTR1)	TTIND6G	SSR1_HUMAN	Inhibitor	[6]
Somatostatin receptor type 2 (SSTR2)	TTZ6T9E	SSR2_HUMAN	Inhibitor	[7]
Somatostatin receptor type 5 (SSTR5)	TT2BC4G	SSR5_HUMAN	Inhibitor	[8]
------------------------------------------------------------------------------------

Pasireotide Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Somatostatin receptor type 5 (SSTR5)	OTWVLRTM	SSR5_HUMAN	Affects Binding	[9]
Somatostatin receptor type 1 (SSTR1)	OTFAGWO7	SSR1_HUMAN	Affects Binding	[9]
Somatostatin receptor type 3 (SSTR3)	OT0B1T93	SSR3_HUMAN	Affects Binding	[9]
Somatostatin receptor type 2 (SSTR2)	OTFN8JM1	SSR2_HUMAN	Affects Binding	[9]
Somatostatin receptor type 4 (SSTR4)	OT2KZCK7	SSR4_HUMAN	Affects Binding	[9]
------------------------------------------------------------------------------------

Indication(s) of Diazoxide

Disease Entry	ICD 11	Status	REF
Congenital hyperinsulinism	5A4Y	Approved	[3]
Hyperinsulinemia	5A4Y	Approved	[3]
Hypertension	BA00-BA04	Approved	[4]
Hypertensive emergency	BA03	Approved	[3]
Insulinoma	2C10.1	Approved	[3]
Malignant essential hypertension	BA00	Approved	[3]

Diazoxide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Potassium channel unspecific (KC)	TT1VOHK	NOUNIPROTAC	Modulator	[10]
------------------------------------------------------------------------------------

Diazoxide Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[11]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[11]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Increases Activity	[12]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Secretion	[11]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[13]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[13]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Increases Expression	[12]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11)	OTPUUELV	KCJ11_HUMAN	Decreases Expression	[14]
------------------------------------------------------------------------------------


⏷ Show the Full List of 8 DOT(s)

References

1	ClinicalTrials.gov (NCT02779257) Pasireotide Treatment for Neuroendocrine Tumor
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	Diazoxide FDA Label
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: 2409).
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. (Target id: 357).
6	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. (Target id: 355).
7	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. (Target id: 356).
8	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. (Target id: 359).
9	Medicinal chemistry of somatostatin analogs leading to the DTPA and DOTA conjugates of the multi-receptor-ligand SOM230. J Endocrinol Invest. 2005;28(11 Suppl International):15-20.
10	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
11	Antihypertensive drugs clonidine, diazoxide, hydralazine and furosemide regulate the production of cytokines by placentas and peripheral blood mononuclear cells in normal pregnancy. J Hypertens. 2006 May;24(5):915-22. doi: 10.1097/01.hjh.0000222762.84605.03.
12	Diazoxide-mediated preconditioning against apoptosis involves activation of cAMP-response element-binding protein (CREB) and NFkappaB. J Biol Chem. 2004 Nov 5;279(45):46748-54. doi: 10.1074/jbc.M406217200. Epub 2004 Aug 23.
13	Diazoxide-mediated growth inhibition in human lung cancer cells via downregulation of beta-catenin-mediated cyclin D1 transcription. Lung. 2009 Jan-Feb;187(1):61-7. doi: 10.1007/s00408-008-9127-1. Epub 2008 Dec 4.
14	Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats. Toxicol Appl Pharmacol. 2013 Feb 1;266(3):375-84. doi: 10.1016/j.taap.2012.11.015. Epub 2012 Nov 28.