Details of the Drug Combination

General Information of Drug Combination (ID: DCW07A5)

• Drug Combination Name: Diethylcarbamazine + Clindamycin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Diethylcarbamazine (DM1TJ8F): Small molecular drug
  Clindamycin (DM15HL8): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 30.77
  Bliss Independence Score: 30.77
  Loewe Additivity Score: 39.46
  LHighest Single Agent (HSA) Score: 39.46

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Diethylcarbamazine

Disease Entry	ICD 11	Status	REF
Elephantiasis	N.A.	Approved	[2]
Loiasis	N.A.	Approved	[2]
Lymphatic filariasis	1F66.3	Approved	[3]
Onchocerciasis	1F6A	Approved	[2]

Diethylcarbamazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Inhibitor	[5]

Diethylcarbamazine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Activity	[6]

Indication(s) of Clindamycin

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[3]
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	[7]

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	[8]
Beta-lactamase (blaB)	DEMSNER	A4LA84_EDWTA	Metabolism	[9]

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	[10]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Expression	[11]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[11]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[12]

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] Diethylcarbamazine FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Clindamycin FDA Label
• [5] Inhibition of leukotriene formation by diethylcarbamazine modifies the acid-base balance in the rabbits with blast injuries of the lungs. Vojnosanit Pregl. 1999 May-Jun;56(3):243-7.
• [6] Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
• [7] Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
• [8] In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos. 2003 Jul;31(7):878-87.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.