Details of the Drug Combination

General Information of Drug Combination (ID: DC10B7U)

• Drug Combination Name: Tranylcypromine + Clindamycin
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  Tranylcypromine (DMGB5RE): Small molecular drug
  Clindamycin (DM15HL8): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 4.027
  Bliss Independence Score: 3.469
  Loewe Additivity Score: 4.167
  LHighest Single Agent (HSA) Score: 5.023

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tranylcypromine

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Approved	[2]
Prostate cancer	2C82.0	Patented	[3]

Tranylcypromine Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	Inhibitor	[3]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[5]
Monoamine oxidase type A (MAO-A)	TT3WG5C	AOFA_HUMAN	Inhibitor	[6]

Tranylcypromine Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2J2 (CYP2J2)	OTJBTEH8	CP2J2_HUMAN	Decreases Activity	[7]
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Decreases Activity	[8]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[9]
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[10]
Cytochrome P450 2B6 (CYP2B6)	OTOYO4S7	CP2B6_HUMAN	Decreases Activity	[11]
Cytochrome P450 2A6 (CYP2A6)	OT52TWG3	CP2A6_HUMAN	Decreases Activity	[12]

Indication(s) of Clindamycin

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[2]
Aspiration pneumonia	N.A.	Approved	[4]
Bacteremia	1A73	Approved	[4]
Bacterial vaginosis	MF3A	Approved	[4]
Pleural empyema	N.A.	Approved	[4]
Staphylococcal pneumonia	N.A.	Approved	[4]
Staphylococcus aureus infection	N.A.	Approved	[4]
Streptococcal pneumonia	N.A.	Approved	[4]
Pelvic inflammatory disease	GA05	Investigative	[4]

Clindamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 50S ribosomal RNA (Bact 50S rRNA)	TTUWYEA	NOUNIPROTAC	Binder	[13]

Clindamycin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]
Beta-lactamase (blaB)	DEMSNER	A4LA84_EDWTA	Metabolism	[15]

Clindamycin Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[16]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Expression	[17]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[17]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[18]

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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
• [4] Clindamycin FDA Label
• [5] Tranylcypromine: new perspectives on an "old" drug. Eur Arch Psychiatry Clin Neurosci. 2006 Aug;256(5):268-73.
• [6] Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice. Int J Neuropsychopharmacol. 2009 Mar 11:1-11.
• [7] In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: different contribution of CYP2J2 in the small intestine and liver. Xenobiotica. 2003 Jun;33(6):615-23.
• [8] Validated assays for human cytochrome P450 activities. Drug Metab Dispos. 2004 Jun;32(6):647-60.
• [9] Drug-drug interactions of Z-338, a novel gastroprokinetic agent, with terfenadine, comparison with cisapride, and involvement of UGT1A9 and 1A8 in the human metabolism of Z-338. Eur J Pharmacol. 2004 Aug 23;497(2):223-31.
• [10] Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15.
• [11] Interactions of sesquiterpenes zederone and germacrone with the human cytochrome P450 system. Toxicol In Vitro. 2013 Sep;27(6):2005-12.
• [12] Mimicking gene defects to treat drug dependence. Ann N Y Acad Sci. 2000;909:233-46. doi: 10.1111/j.1749-6632.2000.tb06685.x.
• [13] Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
• [14] In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos. 2003 Jul;31(7):878-87.
• [15] Comparison of antimicrobial susceptibility, beta-lactamase production, plasmid analysis and serum bactericidal activity in Edwardsiella tarda, E. ictaluri and E. hoshinae. J Med Microbiol. 1993 Oct;39(4):273-81.
• [16] A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97.
• [17] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [18] Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor cell invasion. Toxicol Sci. 2010 Jul;116(1):140-50. doi: 10.1093/toxsci/kfq085. Epub 2010 Mar 25.