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 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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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Modulator	[2]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Gene/Protein Processing	[3]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Gene/Protein Processing	[4]

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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	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.
4	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.
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.