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

General Information of Drug (ID: DMSQ794)

Drug Name
PKI166 Drug Info
Synonyms
PKI-166; CGP-75166; 187724-61-4; NVP-PKI166; CHEMBL1914653; AC1OCFE0; UNII-9RIE5HW38P; 9RIE5HW38P; SCHEMBL177814; GTPL7642; CHEMBL1963502; ZINC23255; AOB1619; PKI-75166; BDBM50358046; NCGC00387215-02; AS-16676; KB-275097; PKI-166, > 4-[4-[[(1R)-1-phenylethyl]amino]-7H-pyrrolo[4,5-e]pyrimidin-6-yl]phenol
Indication
Disease Entry ICD 11 Status REF
Esophageal cancer 2B70 Discontinued in Phase 2 [1]
Cross-matching ID
PubChem CID
6918403
TTD Drug ID
DMSQ794

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Epidermal growth factor receptor (EGFR)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [5]
Lapatinib DM3BH1Y Breast cancer 2C60-2C65 Approved [6]
Gefitinib DM15F0X Colon adenocarcinoma Approved [7]
Erlotinib DMCMBHA Adrenal gland neoplasm Approved [8]
Vandetanib DMRICNP Solid tumour/cancer 2A00-2F9Z Approved [9]
Dacomitinib DMOH8VY Non-small-cell lung cancer 2C25.Y Approved [10]
BIBW 2992 DMTKD7Q Non-small-cell lung cancer 2C25.Y Approved [11]
SKI-758 DMQ8E9R Ischemia 8B10-8B11 Approved [12]
Epidermal growth factor DMVONE6 Vulnerary ND56.Z Approved [10]
Merimepodib DM0HS92 Breast cancer 2C60-2C65 Approved [13]
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Drug(s) Affected By Receptor tyrosine-protein kinase erbB-2 (ERBB2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Trastuzumab DMZQOUX Breast cancer 2C60-2C65 Approved [14]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [15]
Mechlorethamine DM0CVXA Chronic myelogenous leukaemia 2A20.0 Approved [16]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [17]
Gefitinib DM15F0X Colon adenocarcinoma Approved [18]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [19]
Selenium DM25CGV N. A. N. A. Approved [20]
Methotrexate DM2TEOL Anterior urethra cancer Approved [21]
Quercetin DM3NC4M Obesity 5B81 Approved [22]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [23]
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Drug(s) Affected By Solute carrier organic anion transporter family member 1B1 (SLCO1B1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Enalapril DMNFUZR Congestive heart failure BD10 Approved [24]
Lovastatin DM9OZWQ Arteriosclerosis BD40 Approved [25]
Bosentan DMIOGBU Pulmonary arterial hypertension BB01.0 Approved [26]
Repaglinide DM5SXUV Diabetic complication 5A2Y Approved [27]
Methotrexate DM2TEOL Anterior urethra cancer Approved [28]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [29]
Cholic Acid DM7OKQV Cholelithiasis DC11 Approved [30]
Ursodeoxycholic acid DMCUT21 Cholelithiasis DC11 Approved [30]
Hydroxyurea DMOQVU9 Chronic myelogenous leukaemia 2A20.0 Approved [31]
Irinotecan DMP6SC2 Adenocarcinoma 2D40 Approved [32]
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Drug(s) Affected By ATP-binding cassette sub-family C member 2 (ABCC2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Lopinavir DMITQS0 Human immunodeficiency virus infection 1C62 Approved [33]
Sulfinpyrazone DMEV954 Gout FA25 Approved [34]
Probenecid DMMFWOJ Acute gonococcal cervicitis Approved [35]
Docetaxel DMDI269 Advanced cancer 2A00-2F9Z Approved [36]
Methotrexate DM2TEOL Anterior urethra cancer Approved [37]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [38]
Cholic Acid DM7OKQV Cholelithiasis DC11 Approved [39]
Epirubicin DMPDW6T Solid tumour/cancer 2A00-2F9Z Approved [40]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [41]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [42]
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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
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Modulator [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Regulation of Drug Effects [3]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Gene/Protein Processing [4]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Gene/Protein Processing [3]

References

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2 Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomized rats.J Pharmacol Exp Ther.2013 Jun;345(3):393-403.
3 Hepatic transport of PKI166, an epidermal growth factor receptor kinase inhibitor of the pyrrolo-pyrimidine class, and its main metabolite, ACU154. Drug Metab Dispos. 2004 Nov;32(11):1272-8. doi: 10.1124/dmd.104.000497. Epub 2004 Jul 27.
4 Cooperation between fibroblast growth factor receptor-4 and ErbB2 in regulation of cyclin D1 translation. J Biol Chem. 2004 Nov 26;279(48):50004-11. doi: 10.1074/jbc.M404252200. Epub 2004 Sep 17.
5 Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
6 Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
7 Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
8 Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
9 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
10 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: 1797).
11 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
12 Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
13 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
14 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
15 Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers (Basel). 2020 Sep 27;12(10):2774. doi: 10.3390/cancers12102774.
16 Down-regulation of HER-2 expression in human breast cancer cell HBC-4 and ZR75-1 by nitrogen-mustard-N-oxide. Kobe J Med Sci. 2007;53(4):135-42.
17 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.
18 Epidermal growth factor receptor activity determines response of colorectal cancer cells to gefitinib alone and in combination with chemotherapy. Clin Cancer Res. 2005 Oct 15;11(20):7480-9. doi: 10.1158/1078-0432.CCR-05-0328.
19 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
20 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.
21 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
22 Inhibition of prostate cancer cell colony formation by the flavonoid quercetin correlates with modulation of specific regulatory genes. Clin Diagn Lab Immunol. 2004 Jan;11(1):63-9. doi: 10.1128/cdli.11.1.63-69.2004.
23 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
24 Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther. 2011 May;33(5):655-63. doi: 10.1016/j.clinthera.2011.04.018.
25 Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005 Apr;33(4):537-46.
26 Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
27 Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther. 2005 Jun;77(6):468-78. doi: 10.1016/j.clpt.2005.01.018.
28 SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. Toxicol Sci. 2014 Nov;142(1):196-209. doi: 10.1093/toxsci/kfu162. Epub 2014 Aug 14.
29 SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789-99.
30 Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
31 Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
32 Severe toxicities after irinotecan-based chemotherapy in a patient with lung cancer: a homozygote for the SLCO1B1*15 allele. Ther Drug Monit. 2007 Oct;29(5):666-8. doi: 10.1097/FTD.0b013e3181357364.
33 Functional defect caused by the 4544G>A SNP in ABCC2: potential impact for drug cellular disposition. Pharmacogenet Genomics. 2011 Dec;21(12):884-93. doi: 10.1097/FPC.0b013e32834d672b.
34 Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated resistance to chlorambucil cytotoxicity. J Pharmacol Exp Ther. 2004 Jan;308(1):260-7. doi: 10.1124/jpet.103.057729. Epub 2003 Oct 20.
35 MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int J Cancer. 2005 Sep 20;116(5):824-9. doi: 10.1002/ijc.21013.
36 Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia. Cancer Sci. 2008 May;99(5):967-72.
37 Methotrexate normalizes up-regulated folate pathway genes in rheumatoid arthritis. Arthritis Rheum. 2013 Nov;65(11):2791-802.
38 In vitro study of transporters involved in intestinal absorption of inorganic arsenic. Chem Res Toxicol. 2012 Feb 20;25(2):446-53. doi: 10.1021/tx200491f. Epub 2012 Jan 26.
39 Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23.
40 Co-encapsulation of chrysophsin-1 and epirubicin in PEGylated liposomes circumvents multidrug resistance in HeLa cells. Chem Biol Interact. 2015 Dec 5;242:13-23. doi: 10.1016/j.cbi.2015.08.023. Epub 2015 Sep 1.
41 Evaluation of drug transporters' significance for multidrug resistance in head and neck squamous cell carcinoma. Head Neck. 2011 Jul;33(7):959-68. doi: 10.1002/hed.21559. Epub 2010 Aug 24.
42 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.