Details of the Drug Combination

General Information of Drug Combination (ID: DCTWZUZ)

Drug Combination Name
PFK-158 Nizatidine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs PFK-158   DMIR21F Nizatidine   DMGFV3Z
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: 9.5
Bliss Independence Score: 9.5
Loewe Additivity Score: 23.59
LHighest Single Agent (HSA) Score: 23.61

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 [5]
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Indication(s) of Nizatidine
Disease Entry ICD 11 Status REF
Acid-reflux disorder DA22 Approved [3]
Gastric ulcer DA60 Approved [4]
Peptic esophagitis N.A. Approved [4]
Peptic ulcer DA61 Approved [4]
Nizatidine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Histamine H2 receptor (H2R) TTQHJ1K HRH2_HUMAN Antagonist [6]
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Nizatidine Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [8]
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Nizatidine Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Calcitonin (CALCA) OTZ11LHB CALC_HUMAN Increases Expression [9]
Protachykinin-1 (TAC1) OTM842YW TKN1_HUMAN Increases Expression [9]
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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 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: 7248).
4 Nizatidine FDA Label
5 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.
6 Does the use of nizatidine, as a pro-kinetic agent, improve gastric emptying in patients post-oesophagectomy J Gastrointest Surg. 2009 Mar;13(3):432-7.
7 DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB00585)
8 Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
9 Effects of histamine H(2)-receptor antagonists on human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. J Pharm Pharmacol. 2002 Nov;54(11):1559-63. doi: 10.1211/002235702117.