Details of the Drug Combination

General Information of Drug Combination (ID: DCMEBJX)

• Drug Combination Name: Maprotiline + Cilastatin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Maprotiline (DMPWB7T): Small molecular drug
  Cilastatin (DME2H5T): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.26
  Bliss Independence Score: 3.26
  Loewe Additivity Score: 3.94
  LHighest Single Agent (HSA) Score: 3.94

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Maprotiline

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[2]
Major depressive disorder	6A70.3	Approved	[3]
Mixed anxiety and depressive disorder	N.A.	Investigative	[2]

Maprotiline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[6]

Maprotiline Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[7]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[7]

Maprotiline Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases ADR	[8]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[9]

Indication(s) of Cilastatin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[4]
Bacterial infection	1A00-1C4Z	Approved	[5]
Endometritis	N.A.	Approved	[4]
Peritonitis	N.A.	Approved	[4]
Pelvic inflammatory disease	GA05	Investigative	[4]

Cilastatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dehydropeptidase I (DPEP1)	TTYUENF	DPEP1_HUMAN	Inhibitor	[10]

Cilastatin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dipeptidase 1 (DPEP1)	OTVR8V1L	DPEP1_HUMAN	Decreases Activity	[11]

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] Maprotiline FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Cilastatin FDA Label
• [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. (Ligand id: 5166).
• [6] Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets. Gen Physiol Biophys. 2005 Mar;24(1):113-28.
• [7] Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol. 2002 Mar;90(3):144-9.
• [8] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [9] The antidepressants maprotiline and fluoxetine induce Type II autophagic cell death in drug-resistant Burkitt's lymphoma. Int J Cancer. 2011 Apr 1;128(7):1712-23. doi: 10.1002/ijc.25477. Epub 2010 May 25.
• [10] Pharmacokinetic study of pleural fluid penetration of carbapenem antibiotic agents in chemical pleurisy. Respir Med. 2006 Feb;100(2):324-31.
• [11] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.