Details of the Drug Combination

General Information of Drug Combination (ID: DC0CCO2)

• Drug Combination Name: Mesalazine + Everolimus
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Mesalazine (DMOL5IU): Small molecular drug
  Everolimus (DM8X2EH): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 18.74
  Bliss Independence Score: 18.74
  Loewe Additivity Score: 24.79
  LHighest Single Agent (HSA) Score: 24.81

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mesalazine

Disease Entry	ICD 11	Status	REF
Diverticulitis	N.A.	Approved	[2]
Proctitis	DB33.Z	Approved	[3]
Ulcerative colitis	DD71	Approved	[4]
Ulcerative proctosigmoiditis	N.A.	Approved	[5]

Mesalazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Inhibitor	[10]

Mesalazine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[11]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[12]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[12]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[12]

Mesalazine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[13]

Indication(s) of Everolimus

Disease Entry	ICD 11	Status	REF
Advanced cancer	2A00-2F9Z	Approved	[6]
Advanced/metastatic breast cancer	2C60	Approved	[7]
Brainstem neoplasm	N.A.	Approved	[6]
Breast carcinoma	N.A.	Approved	[6]
Graft-versus-host disease	4B24	Approved	[6]
Intracranial meningioma	N.A.	Approved	[6]
Leukemia	N.A.	Approved	[6]
Lung cancer	2C25.0	Approved	[6]
Mucosal melanoma	N.A.	Approved	[6]
Multiple sclerosis	8A40	Approved	[6]
Plasma cell myeloma	2A83.1	Approved	[6]
Prostate cancer	2C82.0	Approved	[6]
Renal cell carcinoma	2C90	Approved	[8]
Salivary gland squamous cell carcinoma	N.A.	Approved	[6]
Tuberous sclerosis	LD2D.2	Approved	[6]
Kidney cancer	2C90.0	Phase 3	[8]
Castration-resistant prostate carcinoma	N.A.	Investigative	[6]
Colon cancer	2B90.Z	Investigative	[6]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[9]
Neuroblastoma	2D11.2	Investigative	[6]
Pancreatic acinar cell carcinoma	N.A.	Investigative	[6]
Polycystic kidney disease	GB8Y	Investigative	[6]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[9]

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	[14]
HUMAN mammalian target of rapamycin (mTOR)	TT7HQAF	MTOR_HUMAN	Inhibitor	[9]

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	[15]

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	[16]

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] Colonic diverticular disease. Nat Rev Dis Primers. 2020 Mar 26;6(1):20.
• [3] Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository. Digestion. 2018;97(1):59-63.
• [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: 4655).
• [5] Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-analysis. J Crohns Colitis. 2021 Jul 5;15(7):1184-1196.
• [6] Everolimus FDA Label
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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. (Ligand id: 5889).
• [9] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [11] Transport studies with 5-aminosalicylate. Eur J Clin Pharmacol. 2006 Oct;62(10):871-5.
• [12] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [13] NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis. Z Gastroenterol. 2008 Mar;46(3):259-65.
• [14] 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.
• [15] 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.
• [16] The evolving experience using everolimus in clinical transplantation. Transplant Proc. 2004 Mar;36(2 Suppl):495S-499S.