Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM5X7VY)

Drug Name
Pyrimethamine Drug Info
Synonyms
Chloridin; Chloridine; Chloridyn; Darachlor; Daraclor; Darapram; Daraprim; Daraprime; Daraprin; Diaminopyritamin; Erbaprelina; Ethylpyrimidine; Khloridin; Malacid; Malocid; Malocide; Maloprim; Pirimecidan; Pirimetamin; Pirimetamina; Primethamine; Pyremethamine; Pyrimethamin; Pyrimethaminum; Tindurin; Tindurine; Tinduring; Aventis Brand of Pyrimethamine; Glaxo Wellcome Brand of Pyrimethamine; GlaxoSmithKline Brand of Pyrimethamine; M alocid; Pirimetamina [Spanish]; Pyrimethamine Hcl; Wellcome Brand of Pyrimethamine; BW 5063; RP 4753; WR 2978; AZT + Pyrimethamine combination; BW 50-63; Daraprim (TN); EXR-101; Lactoferrin B & Pyrimethamine; Lactoferrin H & Pyrimethamine; Pirimetamina [INN-Spanish]; Pyrimethamine (Pyr); Pyrimethaminum [INN-Latin]; TCMDC-123831; TCMDC-125860; CRL-8131 & Pyrimethamine; CRL-8142 & Pyrimethamine; Fansidar (Pyrimethamine/Sulfadoxine); Pyrimethamine (JAN/USP/INN); Pyrimethamine [USAN:INN:BAN:JAN]; 2,4-Diamino-5-(4-chlorophenyl)-6-ethylpyrimidine; 2,4-Diamino-5-(p-chlorophenyl)-6-ethylpyrimidine; 2,4-Diamino-5-chlorophenyl-6-ethylpyrimidine; 5-(4'-Chlorophenyl)-2,4-diamino-6-ethylpyrimidine; 5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE; 5-(4-CHLOROPHENYL)-6-ETHYL-2,4-PYRIMIDINEDIAMINE; 5-(4-Chlorophenyl)-6-ethyl-2,4-diaminopyrimidine; 5-(4-Chlorophenyl)-6-ethyl-2,4-pyrimidi nediamine; 5-(4-chlorophenyl)-2,4-diamino-6-ethylpyrimidine; 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine; 5-(p-chlorophenyl)-6-ethyl-2,4-diaminopyrimidine; 5-[4-Chlorophenyl]-6-ethyl-2,4-pyrimidinediamine
Indication
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [1]
Therapeutic Class
Antimalarials
Cross-matching ID
PubChem CID
4993
ChEBI ID
CHEMBL36
CAS Number
CAS 58-14-0
TTD Drug ID
DM5X7VY
VARIDT Drug ID
DR01272
ACDINA Drug ID
D00573

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Folate receptor alpha (FOLR1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Mirvetuximab soravtansine DM5S4LX Ovarian cancer 2C73 Approved [9]
EC20 DMLA1ER Ovarian cancer 2C73 Phase 3 [10]
MK-8109 DM84LO5 Ovarian cancer 2C73 Phase 3 [11]
Farletuzumab DMFLWX1 Non-small-cell lung cancer 2C25.Y Phase 3 [12]
EC-145 DM0KVJC Solid tumour/cancer 2A00-2F9Z Phase 2 [13]
FolateImmune DMB9ADM Renal cell carcinoma 2C90 Phase 2 [14]
Talotrexin DM1AB4L Solid tumour/cancer 2A00-2F9Z Phase 1/2 [15]
BMS-753493 DMDQO0S Solid tumour/cancer 2A00-2F9Z Phase 1/2 [16]
EC0489 DM8RD4T Solid tumour/cancer 2A00-2F9Z Phase 1 [17]
IMGN-853 DMR8OG2 Solid tumour/cancer 2A00-2F9Z Phase 1 [18]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Breast cancer resistance protein (ABCG2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [19]
Methotrexate DM2TEOL Anterior urethra cancer Approved [20]
Folic Acid DMEMBJC Colorectal carcinoma Approved [21]
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [22]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [23]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [24]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [25]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [24]
Sulfasalazine DMICA9H Irritable bowel syndrome DD91.0 Approved [26]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [27]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Transported By Multidrug and toxin extrusion protein 1 (SLC47A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aciclovir DMYLOVR Genital herpes 1A94 Approved [28]
Metformin DM89QE1 Colorectal carcinoma Approved [29]
Ganciclovir DM1MBYQ Cytomegalovirus infection 1D82 Approved [28]
Cimetidine DMH61ZB Acid-reflux disorder DA22 Approved [28]
Chloroquine DMSI5CB Malaria 1F40-1F45 Approved [30]
Procainamide DMNMXR8 Ventricular arrhythmias BC71 Approved [28]
Topotecan DMP6G8T Central nervous system neoplasm Approved [28]
Cephalexin DMD5JU8 Acute otitis media AB00 Approved [31]
LY2835219 DM93VBZ Breast cancer 2C60-2C65 Approved [32]
Dofetilide DMPN1TW Sinus rhythm disorder BC9Y Approved [33]
Cimetidine DMH61ZB Acid-reflux disorder DA22 Approved [34]
Verapamil DMA7PEW Angina pectoris BA40 Approved [35]
Imipramine DM2NUH3 Depression 6A70-6A7Z Approved [34]
Methotrexate DM2TEOL Anterior urethra cancer Approved [36]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [37]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [38]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [39]
Zoledronate DMIXC7G Adenocarcinoma 2D40 Approved [40]
Quinidine DMLPICK N. A. N. A. Approved [34]
Mebendazole DMO14SG Ascariasis 1F62 Approved [41]
⏷ Show the Full List of 20 Drug(s)
Drug(s) Affected By Protein c-Fos (FOS)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [42]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [43]
Verapamil DMA7PEW Angina pectoris BA40 Approved [8]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [44]
Acebutolol DM0TI4U Hypertension BA00-BA04 Approved [8]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [45]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [46]
Methotrexate DM2TEOL Anterior urethra cancer Approved [47]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [48]
Quercetin DM3NC4M Obesity 5B81 Approved [49]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Histone H2AX (H2AX)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [50]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [51]
Selenium DM25CGV N. A. N. A. Approved [52]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [53]
Etretinate DM2CZFA Keratosis ED56 Approved [54]
Methotrexate DM2TEOL Anterior urethra cancer Approved [55]
Dactinomycin DM2YGNW Adult kidney Wilms tumor Approved [56]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [57]
Lapatinib DM3BH1Y Breast cancer 2C60-2C65 Approved [58]
Quercetin DM3NC4M Obesity 5B81 Approved [59]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By HLA class I histocompatibility antigen, alpha chain G (HLA-G)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Selenium DM25CGV N. A. N. A. Approved [52]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [6]
Methotrexate DM2TEOL Anterior urethra cancer Approved [36]
Omeprazole DM471KJ Cystic fibrosis CA25 Approved [6]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [60]
Erythromycin DM4K7GQ Acne vulgaris ED80 Approved [6]
Isotretinoin DM4QTBN Acne vulgaris ED80 Approved [61]
Lisinopril DMUOK4C Chronic heart failure BD1Z Approved [6]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [6]
Glimepiride DM5FSJA Diabetic complication 5A2Y Approved [6]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Folate receptor alpha (FOLR1) TTVC37M FOLR1_HUMAN Modulator [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug and toxin extrusion protein 1 (SLC47A1) DTZGT0P S47A1_HUMAN Substrate [3]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Post-Translational Modifications [5]
HLA class I histocompatibility antigen, alpha chain G (HLA-G) OTMLK1KN HLAG_HUMAN Gene/Protein Processing [6]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Gene/Protein Processing [7]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Gene/Protein Processing [8]

References

1 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).
2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
3 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.
4 Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
5 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.
6 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.
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 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.
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 EP patent application no. 2822386, Folate receptor alpha binding ligands.
11 A current review of folate receptor alpha as a potential tumor target in non-small-cell lung cancer. Drug Des Devel Ther. 2015; 9: 4989-4996.
12 Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer.Gynecol Oncol.2013 Jun;129(3):452-8.
13 Significance of Folate Receptor alpha and Thymidylate Synthase Protein Expression in Patients with Non-Small Cell Lung Cancer treated with Pemetrexed. J Thorac Oncol. 2013 January; 8(1): 19-30.
14 Responsiveness of the Effective Consumer Scale (EC-17). J Rheumatol. 2009 Sep;36(9):2087-91.
15 Cancer chemotherapy: targeting folic acid synthesis. Cancer Manag Res. 2010; 2: 293-301.
16 A phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493), a folate receptor targeted chemotherapeutic agent in humans with advanced solid tumors. Invest New Drugs. 2015 Apr;33(2):321-31.
17 National Cancer Institute Drug Dictionary (drug id 638649).
18 Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem. 2010 Jan;21(1):84-92.
19 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
20 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
21 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
22 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
23 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
24 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
25 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
26 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
27 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
28 Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
29 Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
30 Molecular mechanism of renal tubular secretion of the antimalarial drug chloroquine. Antimicrob Agents Chemother. 2011 Jul;55(7):3091-8.
31 Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
32 Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
33 FDA Drug Development and Drug Interactions
34 Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney. Drug Metab Dispos. 2006 Nov;34(11):1868-74. doi: 10.1124/dmd.106.010876. Epub 2006 Aug 23.
35 Neonicotinoid pesticides poorly interact with human drug transporters. J Biochem Mol Toxicol. 2019 Oct;33(10):e22379. doi: 10.1002/jbt.22379. Epub 2019 Jul 31.
36 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
37 Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
38 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
39 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
40 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
41 Mebendazole, an antiparasitic drug, inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis. Toxicol In Vitro. 2017 Sep;43:87-91. doi: 10.1016/j.tiv.2017.06.007. Epub 2017 Jun 9.
42 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
43 Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
44 Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
45 Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
46 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
47 Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. Arthritis Res Ther. 2014 Jan 20;16(1):R17. doi: 10.1186/ar4444.
48 Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. Cardiovasc Res. 2005 Aug 1;67(2):333-41. doi: 10.1016/j.cardiores.2005.03.016. Epub 2005 Apr 21.
49 The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem. 2004 Jun 25;279(26):27008-16. doi: 10.1074/jbc.M403588200. Epub 2004 Apr 16.
50 Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
51 Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes. J Toxicol Sci. 2015 Jun;40(3):329-38. doi: 10.2131/jts.40.329.
52 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
53 Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology. 2020 Apr 15;435:152422. doi: 10.1016/j.tox.2020.152422. Epub 2020 Feb 26.
54 Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids. Bioorg Med Chem. 2007 Jul 15;15(14):4863-75. doi: 10.1016/j.bmc.2007.04.057. Epub 2007 May 3.
55 Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2. Biochem Pharmacol. 2011 Feb 15;81(4):510-7. doi: 10.1016/j.bcp.2010.11.014. Epub 2010 Nov 27.
56 Actinomycin D inhibits the expression of the cystine/glutamate transporter xCT via attenuation of CD133 synthesis in CD133(+) HCC. Chem Biol Interact. 2019 Aug 25;309:108713. doi: 10.1016/j.cbi.2019.06.026. Epub 2019 Jun 19.
57 Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells. Ann Hematol. 2010 Nov;89(11):1115-24. doi: 10.1007/s00277-010-0988-z. Epub 2010 May 25.
58 The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
59 The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX. DNA Repair (Amst). 2004 Mar 4;3(3):235-44. doi: 10.1016/j.dnarep.2003.10.014.
60 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
61 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.