Details of the Drug Combination

General Information of Drug Combination (ID: DCKCGE2)

• Drug Combination Name: Clindamycin + Pepstatin
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Clindamycin (DM15HL8): Small molecular drug
  Pepstatin (DM9S1EA): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 12.08
  Bliss Independence Score: 12.08
  Loewe Additivity Score: 22.82
  LHighest Single Agent (HSA) Score: 22.82

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	[5]

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	[6]
Beta-lactamase (blaB)	DEMSNER	A4LA84_EDWTA	Metabolism	[7]

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	[8]
HLA class II histocompatibility antigen, DRB1 beta chain (HLA-DRB1)	OTRGGIFP	DRB1_HUMAN	Affects Expression	[9]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[9]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[10]

Indication(s) of Pepstatin

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Terminated	[4]

Pepstatin Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium Cysteine protease falcipain-2 (Malaria CPF2)	TT7EASG	Q9N6S8_PLAFA	Inhibitor	[11]
Plasmodium Plasmepsin 2 (Malaria PLA2)	TTXMNHO	PLM2_PLAFA	Inhibitor	[12]
Plasmodium Plasmepsin 1 (Malaria PLA1)	TTH9VL3	PLM1_PLAFA	Inhibitor	[12]
Plasmodium Cysteine protease falcipain (Malaria CPF)	TTJNPTK	NOUNIPROTAC	Inhibitor	[12]

Pepstatin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cathepsin D (CTSD)	OTQZ36F3	CATD_HUMAN	Decreases Activity	[13]

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] Clindamycin FDA Label
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004280)
• [5] Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature. 2001 Oct 25;413(6858):814-21.
• [6] In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos. 2003 Jul;31(7):878-87.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
• [12] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [13] Evidence of a lysosomal pathway for apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells. Cell Death Differ. 2001 May;8(5):477-85. doi: 10.1038/sj.cdd.4400843.