Details of the Drug Combination

General Information of Drug Combination (ID: DC0P334)

Drug Combination Name
PFK-158 Sulfinpyrazone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs PFK-158   DMIR21F Sulfinpyrazone   DMEV954
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 13.68
Bliss Independence Score: 13.68
Loewe Additivity Score: 28.57
LHighest Single Agent (HSA) Score: 28.57

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PFK-158
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
PFK-158 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Renal carcinoma antigen NY-REN-56 (PFKFB3) TTTHMQJ F263_HUMAN Inhibitor [4]
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Indication(s) of Sulfinpyrazone
Disease Entry ICD 11 Status REF
Gout FA25 Approved [3]
Sulfinpyrazone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 1 (ABCC1) TTOI92F MRP1_HUMAN Modulator [5]
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Sulfinpyrazone Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [6]
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Sulfinpyrazone 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]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [8]
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Sulfinpyrazone Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2) OTC5U0N5 NR1I2_HUMAN Increases Activity [7]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [9]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 ClinicalTrials.gov (NCT02044861) Phase 1 Safety Study of ACT-PFK-158, 2HCl in Patients With Advanced Solid Malignancies. U.S. National Institutes of Health.
3 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: 5826).
4 Discovery of a PFKFB3 inhibitor for phase I trial testing that synergizes with the B-Raf inhibitor vemurafenib. Cancer Metab. 2014; 2(Suppl 1): P14.
5 Species-dependent transport and modulation properties of human and mouse multidrug resistance protein 2 (MRP2/Mrp2, ABCC2/Abcc2). Drug Metab Dispos. 2008 Apr;36(4):631-40.
6 Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83.
7 CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab Dispos. 2002 Jul;30(7):795-804.
8 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.