Details of the Drug Combination

General Information of Drug Combination (ID: DCNB7G5)

• Drug Combination Name: Octreotide + Motesanib
• Indication: Gastrointestinal Carcinoid Tumor; Status: Phase 1 [1]
• Component Drugs:
  Octreotide (DMHIDCJ): Small molecular drug
  Motesanib (DMZAL8C): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Octreotide

Disease Entry	ICD 11	Status	REF
Acromegaly	5A60.0	Approved	[2]
Carcinoid syndrome	5B10	Approved	[3]
Diabetic retinopathy	9B71.0	Approved	[3]
Neuroendocrine cancer	2B72.1	Investigative	[3]

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	[6]

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	[7]

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	[8]
Glycoprotein hormones alpha chain (CGA)	OT00U3Y3	GLHA_HUMAN	Decreases Secretion	[9]
Thyrotropin subunit beta (TSHB)	OTFDI39D	TSHB_HUMAN	Decreases Secretion	[10]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Affects Expression	[11]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Decreases Expression	[12]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[13]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[14]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Expression	[15]
Cholecystokinin (CCK)	OT1GCG0L	CCKN_HUMAN	Decreases Secretion	[16]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[17]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[18]
Tumor necrosis factor ligand superfamily member 6 (FASLG)	OTZARCHH	TNFL6_HUMAN	Increases Expression	[17]
Somatostatin (SST)	OTY75GQH	SMS_HUMAN	Decreases Secretion	[18]

Indication(s) of Motesanib

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Discontinued in Phase 3	[4]

Motesanib Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[19]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[19]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[19]

References

• [1] ClinicalTrials.gov (NCT00427349) AMG 706 and Octreotide in Treating Patients With Low-Grade Neuroendocrine Tumors
• [2] 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).
• [3] Octreotide 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: 5660).
• [5] [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.
• [6] 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.
• [7] P-glycoprotein- and mrp2-mediated octreotide transport in renal proximal tubule. Br J Pharmacol. 2000 Jan;129(2):251-6.
• [8] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [9] 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.
• [10] 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.
• [11] Long-term treatment of acromegaly with a long-acting analogue of somatostatin, octreotide. Q J Med. 1990 Feb;74(274):189-201.
• [12] 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.
• [13] 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.
• [14] [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.
• [15] Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects. J Clin Pharmacol. 2000 May;40(5):475-81. doi: 10.1177/00912700022009242.
• [16] 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.
• [17] [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.
• [18] 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.
• [19] Clinical pipeline report, company report or official report of Amgen (2009).