Details of the Drug Combination

General Information of Drug Combination (ID: DCNH19Z)

• Drug Combination Name: Everolimus + Octreotide
• Indication: Recurrent Meningiomas; Status: Phase 2 [1]
• Component Drugs:
  Everolimus (DM8X2EH): Small molecular drug
  Octreotide (DMHIDCJ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Everolimus

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[2]
Advanced/metastatic breast cancer	2C60	Approved	[3]
Brainstem neoplasm	N.A.	Approved	[2]
Breast carcinoma	N.A.	Approved	[2]
Graft-versus-host disease	4B24	Approved	[2]
Intracranial meningioma	N.A.	Approved	[2]
Leukemia	N.A.	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Mucosal melanoma	N.A.	Approved	[2]
Multiple sclerosis	8A40	Approved	[2]
Plasma cell myeloma	2A83.1	Approved	[2]
Prostate cancer	2C82.0	Approved	[2]
Renal cell carcinoma	2C90	Approved	[4]
Salivary gland squamous cell carcinoma	N.A.	Approved	[2]
Tuberous sclerosis	LD2D.2	Approved	[2]
Kidney cancer	2C90.0	Phase 3	[4]
Castration-resistant prostate carcinoma	N.A.	Investigative	[2]
Colon cancer	2B90.Z	Investigative	[2]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[5]
Neuroblastoma	2D11.2	Investigative	[2]
Pancreatic acinar cell carcinoma	N.A.	Investigative	[2]
Polycystic kidney disease	GB8Y	Investigative	[2]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[5]

Everolimus Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[8]
HUMAN mammalian target of rapamycin (mTOR)	TT7HQAF	MTOR_HUMAN	Inhibitor	[5]

Everolimus Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Everolimus Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

Indication(s) of Octreotide

Disease Entry	ICD 11	Status	REF
Acromegaly	5A60.0	Approved	[6]
Carcinoid syndrome	5B10	Approved	[7]
Diabetic retinopathy	9B71.0	Approved	[7]
Neuroendocrine cancer	2B72.1	Investigative	[7]

Octreotide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Somatostatin receptor type 2 (SSTR2)	TTZ6T9E	SSR2_HUMAN	Binder	[12]

Octreotide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[13]

Octreotide Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[14]
Glycoprotein hormones alpha chain (CGA)	OT00U3Y3	GLHA_HUMAN	Decreases Secretion	[15]
Thyrotropin subunit beta (TSHB)	OTFDI39D	TSHB_HUMAN	Decreases Secretion	[16]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Affects Expression	[17]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Decreases Expression	[18]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[19]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[20]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Expression	[21]
Cholecystokinin (CCK)	OT1GCG0L	CCKN_HUMAN	Decreases Secretion	[22]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[23]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[24]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[23]
Somatostatin (SST)	OTY75GQH	SMS_HUMAN	Decreases Secretion	[24]

References

• [1] ClinicalTrials.gov (NCT02333565) Combination of Everolimus and Octreotide LAR in Aggressive Recurrent Meningiomas
• [2] Everolimus FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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: 5889).
• [5] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [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. (Ligand id: 2055).
• [7] Octreotide FDA Label
• [8] Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
• [9] Closer to the Site of Action: Everolimus Concentrations in Peripheral Blood Mononuclear Cells Correlate Well With Whole Blood Concentrations. Ther Drug Monit. 2015 Oct;37(5):675-80.
• [10] The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.
• [11] [Effects of octreotide on necrosis of hepatocellular carcinoma xenografts in nude mice]. Ai Zheng. 2009 Jul;28(7):673-8. doi: 10.5732/cjc.009.10055.
• [12] Versatile conjugation of octreotide to dendrimers by cycloaddition ("click") chemistry to yield high-affinity multivalent cyclic Peptide dendrimers. Bioconjug Chem. 2009 Jul;20(7):1323-31.
• [13] P-glycoprotein- and mrp2-mediated octreotide transport in renal proximal tubule. Br J Pharmacol. 2000 Jan;129(2):251-6.
• [14] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [15] Treatment of thyroid-stimulating hormone-secreting adenomas with octreotide. Metabolism. 1992 Sep;41(9 Suppl 2):62-5. doi: 10.1016/0026-0495(92)90033-7.
• [16] Long-term efficacy and tolerability of octreotide treatment in acromegaly. Metabolism. 1992 Sep;41(9 Suppl 2):44-50. doi: 10.1016/0026-0495(92)90030-e.
• [17] Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide. Q J Med. 1990 Feb;74(274):189-201.
• [18] Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients. Eur J Clin Invest. 1992 Jul;22(7):494-502. doi: 10.1111/j.1365-2362.1992.tb01496.x.
• [19] Effect of the somatostatin analogue, octreotide, on exercise-induced hypotension in human subjects with chronic sympathetic failure. Clin Sci (Lond). 1995 Oct;89(4):367-73. doi: 10.1042/cs0890367.
• [20] [Inhibitory effect of somatostatin analogue octreotide on the expression of p53 and Ras in human gastric cancer]. Nan Fang Yi Ke Da Xue Xue Bao. 2011 Jun;31(7):1245-8.
• [21] Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects. J Clin Pharmacol. 2000 May;40(5):475-81. doi: 10.1177/00912700022009242.
• [22] Severe impairment of postprandial cholecystokinin release and gall-bladder emptying and high risk of gallstone formation in acromegalic patients during Sandostatin LAR. Aliment Pharmacol Ther. 2001 Feb;15(2):181-5. doi: 10.1046/j.1365-2036.2001.00924.x.
• [23] [Octreotide induces apoptosis of human hepatoma cells by the mechanism of facilitating the Fas/FasL gene expression therein]. Zhonghua Yi Xue Za Zhi. 2008 Mar 11;88(10):716-8.
• [24] Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma. Endocr Relat Cancer. 2006 Mar;13(1):79-93. doi: 10.1677/erc.1.00988.