Details of the Drug Combination

General Information of Drug Combination (ID: DCTQ8AF)

• Drug Combination Name: Fosfomycin + Pomalidomide
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Fosfomycin (DMVGPMX): Small molecular drug
  Pomalidomide (DMTGBAX): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 11.63
  Bliss Independence Score: 11.63
  Loewe Additivity Score: 25.78
  LHighest Single Agent (HSA) Score: 25.8

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fosfomycin

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[2]
Urinary tract infection	GC08	Approved	[3]

Fosfomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial UDP-N-acetylglucosamine carboxyvinyltransferase (Bact murA)	TTICX3S	MURA_ECOLI	Inhibitor	[6]

Fosfomycin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase alpha-1 (GSTA1)	DE4ZHS1	GSTA1_HUMAN	Metabolism	[7]

Fosfomycin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Decreases Expression	[8]

Indication(s) of Pomalidomide

Disease Entry	ICD 11	Status	REF
Plasma cell myeloma	2A83.1	Approved	[4]
Systemic sclerosis	4A42	Approved	[5]

Pomalidomide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiogenesis/myeloma cell growth (AMCG)	TTDIBYJ	NOUNIPROTAC	Modulator	[9]

Pomalidomide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

Pomalidomide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[12]

Pomalidomide Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Secretion	[13]
Erythroid transcription factor (GATA1)	OTX1R7O1	GATA1_HUMAN	Decreases Expression	[13]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Decreases Expression	[13]
Transcription factor PU.1 (SPI1)	OTVCA1D0	SPI1_HUMAN	Increases Expression	[13]
Endothelial transcription factor GATA-2 (GATA2)	OTBP2QQ2	GATA2_HUMAN	Decreases Expression	[13]
DNA-binding protein inhibitor ID-1 (ID1)	OTKGNZN5	ID1_HUMAN	Increases Expression	[13]
CCAAT/enhancer-binding protein alpha (CEBPA)	OTOM9OE4	CEBPA_HUMAN	Increases Expression	[13]
CCAAT/enhancer-binding protein delta (CEBPD)	OTNBIPMY	CEBPD_HUMAN	Increases Expression	[13]
Krueppel-like factor 1 (KLF1)	OT1FK08U	KLF1_HUMAN	Decreases Expression	[13]
CCAAT/enhancer-binding protein epsilon (CEBPE)	OTKZA25M	CEBPE_HUMAN	Increases Expression	[13]
Transcription factor NF-E2 45 kDa subunit (NFE2)	OTLM94BI	NFE2_HUMAN	Decreases Expression	[13]
Zinc finger protein Gfi-1b (GFI1B)	OTRDW8YO	GFI1B_HUMAN	Decreases Expression	[13]
Zinc finger protein Gfi-1 (GFI1)	OT9HB9H8	GFI1_HUMAN	Increases Expression	[13]
Sal-like protein 4 (SALL4)	OTC08PR5	SALL4_HUMAN	Affects Binding	[14]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Increases Oxidation	[15]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [2] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [3] Fosfomycin FDA Label
• [4] Pomalidomide 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: 7348).
• [6] Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63.
• [7] Formation of an adduct between fosfomycin and glutathione: a new mechanism of antibiotic resistance in bacteria. Antimicrob Agents Chemother. 1988 Oct;32(10):1552-6.
• [8] [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy]. Nihon Jinzo Gakkai Shi. 2003;45(1):37-41.
• [9] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [10] DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB08910)
• [11] Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78.
• [12] Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72.
• [13] Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
• [14] Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome. Elife. 2018 Aug 1;7:e38430. doi: 10.7554/eLife.38430.
• [15] Human cytochrome P450 oxidation of 5-hydroxythalidomide and pomalidomide, an amino analogue of thalidomide. Chem Res Toxicol. 2014 Jan 21;27(1):147-56. doi: 10.1021/tx4004215. Epub 2013 Dec 24.