General Information of Drug Combination (ID: DC13WUT)

Drug Combination Name
Pyrimethamine T-3.5
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Pyrimethamine   DM5X7VY T-3.5   DM3Q1HL
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 2.781
Bliss Independence Score: 0.41
Loewe Additivity Score: 0.198
LHighest Single Agent (HSA) Score: 0.003

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pyrimethamine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [2]
Pyrimethamine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Folate receptor alpha (FOLR1) TTVC37M FOLR1_HUMAN Modulator [4]
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Pyrimethamine Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [5]
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [6]
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Pyrimethamine Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Activity [7]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [8]
Glutathione S-transferase P (GSTP1) OTLP0A0Y GSTP1_HUMAN Decreases Activity [9]
Suppressor of cytokine signaling 3 (SOCS3) OTY183WJ SOCS3_HUMAN Decreases Expression [10]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [11]
Beta-hexosaminidase subunit beta (HEXB) OTROYLCR HEXB_HUMAN Affects Binding [12]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Increases Activity [13]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Phosphorylation [14]
HLA class I histocompatibility antigen, alpha chain G (HLA-G) OTMLK1KN HLAG_HUMAN Affects Expression [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [16]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [16]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [13]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Increases Activity [13]
Multidrug and toxin extrusion protein 2 (SLC47A2) OTF2CNRD S47A2_HUMAN Decreases Activity [7]
Proton-coupled folate transporter (SLC46A1) OT049V7Y PCFT_HUMAN Decreases Activity [17]
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⏷ Show the Full List of 15 DOT(s)
Indication(s) of T-3.5
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Investigative [3]

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 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: 4800).
3 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
5 Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
6 Expression of Organic Anion Transporter 1 or 3 in Human Kidney Proximal Tubule Cells Reduces Cisplatin Sensitivity. Drug Metab Dispos. 2018 May;46(5):592-599.
7 Interactions between Oroxylin A with the solute carrier transporters and ATP-binding cassette transporters: Drug transporters profile for this flavonoid. Chem Biol Interact. 2020 Jun 1;324:109097. doi: 10.1016/j.cbi.2020.109097. Epub 2020 Apr 16.
8 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.
9 Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
10 The antimicrobial drug pyrimethamine inhibits STAT3 transcriptional activity by targeting the enzyme dihydrofolate reductase. J Biol Chem. 2022 Feb;298(2):101531. doi: 10.1016/j.jbc.2021.101531. Epub 2021 Dec 23.
11 Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
12 Crystal structure of -hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone. J Med Chem. 2011 Mar 10;54(5):1421-9. doi: 10.1021/jm101443u. Epub 2011 Jan 25.
13 Pyrimethamine induces apoptosis of melanoma cells via a caspase and cathepsin double-edged mechanism. Cancer Res. 2008 Jul 1;68(13):5291-300. doi: 10.1158/0008-5472.CAN-08-0222.
14 Antifolate activity of pyrimethamine enhances temozolomide-induced cytotoxicity in melanoma cells. Mol Cancer Res. 2009 May;7(5):703-12. doi: 10.1158/1541-7786.MCR-08-0263. Epub 2009 May 12.
15 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.
16 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
17 The human proton-coupled folate transporter (hPCFT): modulation of intestinal expression and function by drugs. Am J Physiol Gastrointest Liver Physiol. 2010 Feb;298(2):G248-54. doi: 10.1152/ajpgi.00224.2009. Epub 2009 Sep 17.