Details of the Drug Combination

General Information of Drug Combination (ID: DC4M05T)

• Drug Combination Name: Suramin + SB-612111
• Indication: DD2; Status: Investigative [1]
• Component Drugs:
  Suramin (DMTOUY9): Small molecular drug
  SB-612111 (DM2SZ3F): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DD2
  Zero Interaction Potency (ZIP) Score: 15.212
  Bliss Independence Score: 15.906
  Loewe Additivity Score: 8.225
  LHighest Single Agent (HSA) Score: 5.852

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Suramin

Disease Entry	ICD 11	Status	REF
African trypanosomiasis	1F51	Phase 1	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[3]

Suramin Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Heparanase (HPSE)	TTR7GJO	HPSE_HUMAN	Inhibitor	[5]
Follicle-stimulating hormone receptor (FSHR)	TTZFDBT	FSHR_HUMAN	Antagonist	[6]
COVID-19 RNA-directed RNA polymerase (RdRp)	TTV1095	R1AB_SARS2 (4393-5324)	Inhibitor	[3]

Suramin Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[7]
Cytochrome P450 2C19 (CYP2C19)	OTFMJYYE	CP2CJ_HUMAN	Decreases Activity	[7]
Hematopoietic prostaglandin D synthase (HPGDS)	OTU8FWHU	HPGDS_HUMAN	Decreases Activity	[8]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[9]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Increases Expression	[10]
Fibroblast growth factor 5 (FGF5)	OTQXGHBY	FGF5_HUMAN	Increases Expression	[10]
Fibroblast growth factor 7 (FGF7)	OTGK6ANL	FGF7_HUMAN	Affects Localization	[11]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Activity	[9]
SHC-transforming protein 1 (SHC1)	OT1J5IRN	SHC1_HUMAN	Increases Expression	[12]
Interleukin-12 subunit beta (IL12B)	OT0JF8A3	IL12B_HUMAN	Increases Expression	[9]

Indication(s) of SB-612111

Disease Entry	ICD 11	Status	REF
Inflammation	1A00-CA43.1	Investigative	[4]

SB-612111 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nociceptin receptor (OPRL1)	TTNT7K8	OPRX_HUMAN	Antagonist	[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] Arsenicals (Melarsoprol), Pentamidine and Suramin in the Treatment of Human African Trypanosomiasis. Parasitol Res. 2003 May;90(1):71-9.
• [3] Suramin, Penciclovir and Anidulafungin bind nsp12, which governs the RNA-dependent-RNA polymerase activity of SARS-CoV-2, with higher interaction energy than Remdesivir, indicating potential in the treatment of Covid-19 infection. April.21.2020. Doi: 10.31219/osf.io/urxwh
• [4] 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: 1693).
• [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: 1728).
• [6] Suramin: clinical uses and structure-activity relationships. Mini Rev Med Chem. 2008 Nov;8(13):1384-94.
• [7] 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.
• [8] Identification of new inhibitors for human hematopoietic prostaglandin D2 synthase among FDA-approved drugs and other compounds. Chem Biol Interact. 2015 Mar 5;229:91-9. doi: 10.1016/j.cbi.2015.01.014. Epub 2015 Jan 17.
• [9] Biological inactivation and impaired detection of IL-10 by suramin. J Immunol Methods. 2005 Apr;299(1-2):91-8. doi: 10.1016/j.jim.2005.01.008. Epub 2005 Feb 17.
• [10] Increased expression of fibroblast growth factors (FGFs) and their receptor by protamine and suramin on Kaposi's sarcoma-derived cells. Anticancer Res. 1993 Jul-Aug;13(4):887-90.
• [11] Keratinocyte growth factor-1 expression in healthy and diseased human periodontal tissues. J Periodontal Res. 2005 Apr;40(2):118-28. doi: 10.1111/j.1600-0765.2004.00780.x.
• [12] Repression of P66Shc expression by SIRT1 contributes to the prevention of hyperglycemia-induced endothelial dysfunction. Circ Res. 2011 Sep 2;109(6):639-48. doi: 10.1161/CIRCRESAHA.111.243592. Epub 2011 Jul 21.
• [13] 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. (Target id: 320).