Details of the Drug Combination

General Information of Drug Combination (ID: DCQB2UD)

• Drug Combination Name: Everolimus + Pasireotide
• Indication: Neuroendocrine Tumors; Status: Phase 1 [1]
• Component Drugs:
  Everolimus (DM8X2EH): Small molecular drug
  Pasireotide (DMHM7JS): 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	[6]
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	[7]

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	[8]

Indication(s) of Pasireotide

Disease Entry	ICD 11	Status	REF
Cushing disease	5A70	Approved	[3]

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	[9]
Somatostatin receptor type 1 (SSTR1)	TTIND6G	SSR1_HUMAN	Inhibitor	[10]
Somatostatin receptor type 2 (SSTR2)	TTZ6T9E	SSR2_HUMAN	Inhibitor	[11]
Somatostatin receptor type 5 (SSTR5)	TT2BC4G	SSR5_HUMAN	Inhibitor	[12]

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	[13]
Somatostatin receptor type 1 (SSTR1)	OTFAGWO7	SSR1_HUMAN	Affects Binding	[13]
Somatostatin receptor type 3 (SSTR3)	OT0B1T93	SSR3_HUMAN	Affects Binding	[13]
Somatostatin receptor type 2 (SSTR2)	OTFN8JM1	SSR2_HUMAN	Affects Binding	[13]
Somatostatin receptor type 4 (SSTR4)	OT2KZCK7	SSR4_HUMAN	Affects Binding	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Castrate Resistant Prostate Cancer	DCYC3YR	N. A.	Phase 1	[14]

References

• [1] ClinicalTrials.gov (NCT01469572) Pasireotide, Everolimus and Selective Internal Radioembolization Therapy for Unresectable Hepatic Metastases
• [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] 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.
• [7] 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.
• [8] The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.
• [9] 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).
• [10] 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).
• [11] 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).
• [12] 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).
• [13] 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.
• [14] ClinicalTrials.gov (NCT01313559) Pasireotide (SOM230) With or Without Everolimus in Treating Patients With Hormone Resistant, Chemotherapy Naive Prostate Cancer