Details of the Drug Combination

General Information of Drug Combination (ID: DCFZ98T)

• Drug Combination Name: Clindamycin + Vancomycin
• Indication: Pre-Diabetes; Status: Phase 2 [1]
• Component Drugs:
  Clindamycin (DM15HL8): Small molecular drug
  Vancomycin (DM3JFIH): N.A.

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Clindamycin

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[2]
Aspiration pneumonia	N.A.	Approved	[3]
Bacteremia	1A73	Approved	[3]
Bacterial vaginosis	MF3A	Approved	[3]
Pleural empyema	N.A.	Approved	[3]
Staphylococcal pneumonia	N.A.	Approved	[3]
Staphylococcus aureus infection	N.A.	Approved	[3]
Streptococcal pneumonia	N.A.	Approved	[3]
Pelvic inflammatory disease	GA05	Investigative	[3]

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	[6]

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	[7]
Beta-lactamase (blaB)	DEMSNER	A4LA84_EDWTA	Metabolism	[8]

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	[9]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Expression	[10]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[10]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[11]

Indication(s) of Vancomycin

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[4]
Bacterial endocarditis	N.A.	Approved	[4]
Clostridioides difficile infection	1A04	Approved	[4]
Methicillin-resistant staphylococci infection	1A00-1A09	Approved	[2]
Neonatal sepsis	N.A.	Approved	[4]
Staphylococcal pneumonia	N.A.	Approved	[4]
Staphylococcus aureus infection	N.A.	Approved	[4]
MRSA infection	1D01.0Y	Investigative	[5]
Skin infection	1F28-1G0Z	Investigative	[4]

Vancomycin Interacts with 14 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
VanA ligase (vanA)	DEOFMQ7	Q0WYK7_ENTFL	Metabolism	[12]
VanA ligase (vanA)	DEO97D6	VANA_ENTFC	Metabolism	[12]
VanB ligase (vanB)	DE27YVU	Q58F99_ENTFC	Metabolism	[12]
VanC2 ligase (vanC)	DEIF4P9	VANC_ENTGA	Metabolism	[13]
VanG ligase (vanG)	DEPH3S7	A0A076ZC24_STRAP	Metabolism	[14]
VanA ligase (vanA)	DEO8E75	A0A437UFE2_ENTAV	Metabolism	[12]
VanB ligase (vanB)	DER7KFQ	VANB_ENTFA	Metabolism	[12]
VanC2 ligase (vanC)	DEH73ZC	Q47720_ENTCA	Metabolism	[15]
D-alanylalanine synthetase (ddl)	DE035GU	A0A1Q6S944_9FIRM	Metabolism	[14]
VanG ligase (vanG)	DEPN8F9	A0A076YRI6_STRAG	Metabolism	[14]
VanB ligase (vanB)	DEMDEJ8	Q58F99_ENTFC	Metabolism	[16]
VanB ligase (vanB)	DE2GMEK	Q58F99_ENTFC	Metabolism	[16]
VanA ligase (vanA)	DEN6VO0	A0A376GZ73_ENTGA	Metabolism	[17]
VanA ligase (vanA)	DESOXHP	A0A4U9YK96_ENTCA	Metabolism	[18], [17]

Vancomycin Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Affects Expression	[10]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[19]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)	OT17HGXJ	DMB_HUMAN	Affects Expression	[10]
Major histocompatibility complex class I-related gene protein (MR1)	OTZU3XX7	HMR1_HUMAN	Affects Expression	[10]

References

• [1] ClinicalTrials.gov (NCT02730962) Interventional Bioremediation of Microbiota in Metabolic Syndrome
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Clindamycin FDA Label
• [4] Vancomycin FDA Label
• [5] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [6] Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
• [7] In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos. 2003 Jul;31(7):878-87.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob Agents Chemother. 1993 Aug;37(8):1563-71.
• [13] Sequence of the vanC gene of Enterococcus gallinarum BM4174 encoding a D-alanine:D-alanine ligase-related protein necessary for vancomycin resistance. Gene. 1992 Mar 1;112(1):53-8.
• [14] vanG element insertions within a conserved chromosomal site conferring vancomycin resistance to Streptococcus agalactiae and Streptococcus anginosus. mBio. 2014 Jul 22;5(4):e01386-14.
• [15] Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10040-4.
• [16] vanI: a novel D-Ala-D-Lac vancomycin resistance gene cluster found in Desulfitobacterium hafniense. Microb Biotechnol. 2014 Sep;7(5):456-66.
• [17] Emergence of high-level resistance to glycopeptides in Enterococcus gallinarum and Enterococcus casseliflavus. Antimicrob Agents Chemother. 1994 Jul;38(7):1675-7.
• [18] vanA in Enterococcus faecium, Enterococcus faecalis, and Enterococcus casseliflavus detected in French cattle. Foodborne Pathog Dis. 2009 Nov;6(9):1107-11.
• [19] [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy]. Nihon Jinzo Gakkai Shi. 2003;45(1):37-41.