Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1FHGQS)

DOT Name Platelet basic protein (PPBP)
Synonyms PBP; C-X-C motif chemokine 7; Leukocyte-derived growth factor; LDGF; Macrophage-derived growth factor; MDGF; Small-inducible cytokine B7
Gene Name PPBP
Related Disease
Arthritis ( )
Hyperlipidemia ( )
Rheumatoid arthritis ( )
Sickle-cell anaemia ( )
Acute coronary syndrome ( )
Advanced cancer ( )
Allergy ( )
Asthma ( )
Atopic dermatitis ( )
Atrial fibrillation ( )
Breast neoplasm ( )
Cardiac failure ( )
Cholangiocarcinoma ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Coronary atherosclerosis ( )
Depression ( )
Diabetic kidney disease ( )
High blood pressure ( )
Influenza ( )
leukaemia ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Non-small-cell lung cancer ( )
Osteoporosis ( )
Psoriasis ( )
Renal cell carcinoma ( )
Sjogren syndrome ( )
Systemic lupus erythematosus ( )
Vitamin B12 deficiency ( )
Tuberculosis ( )
Breast cancer ( )
Breast carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Coronary heart disease ( )
Gastric cancer ( )
Lung squamous cell carcinoma ( )
Parkinson disease ( )
Stomach cancer ( )
Type-1 diabetes ( )
Wilms tumor ( )
UniProt ID
CXCL7_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1F9P; 1NAP; 1TVX
Pfam ID
PF00048
Sequence
MSLRLDTTPSCNSARPLHALQVLLLLSLLLTALASSTKGQTKRNLAKGKEESLDSDLYAE
LRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIATLKDGRKICLDPDAPRIKKIVQKK
LAGDESAD
Function
LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates the formation and secretion of plasminogen activator by human synovial cells. NAP-2 is a ligand for CXCR1 and CXCR2, and NAP-2, NAP-2(73), NAP-2(74), NAP-2(1-66), and most potent NAP-2(1-63) are chemoattractants and activators for neutrophils. TC-1 and TC-2 are antibacterial proteins, in vitro released from activated platelet alpha-granules. CTAP-III(1-81) is more potent than CTAP-III desensitize chemokine-induced neutrophil activation.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )
Viral protein interaction with cytokine and cytokine receptor (hsa04061 )
Chemokine sig.ling pathway (hsa04062 )
Reactome Pathway
Chemokine receptors bind chemokines (R-HSA-380108 )
G alpha (i) signalling events (R-HSA-418594 )
Neutrophil degranulation (R-HSA-6798695 )
Platelet degranulation (R-HSA-114608 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arthritis DIST1YEL Definitive Altered Expression [1]
Hyperlipidemia DIS61J3S Definitive Biomarker [2]
Rheumatoid arthritis DISTSB4J Definitive Altered Expression [1]
Sickle-cell anaemia DIS5YNZB Definitive Biomarker [3]
Acute coronary syndrome DIS7DYEW Strong Biomarker [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Allergy DIS48ZAP Strong Biomarker [6]
Asthma DISW9QNS Strong Altered Expression [7]
Atopic dermatitis DISTCP41 Strong Altered Expression [8]
Atrial fibrillation DIS15W6U Strong Biomarker [9]
Breast neoplasm DISNGJLM Strong Biomarker [10]
Cardiac failure DISDC067 Strong Genetic Variation [11]
Cholangiocarcinoma DIS71F6X Strong Altered Expression [5]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [12]
Colon cancer DISVC52G Strong Biomarker [13]
Colon carcinoma DISJYKUO Strong Biomarker [13]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [14]
Congestive heart failure DIS32MEA Strong Genetic Variation [11]
Coronary atherosclerosis DISKNDYU Strong Biomarker [15]
Depression DIS3XJ69 Strong Altered Expression [16]
Diabetic kidney disease DISJMWEY Strong Biomarker [17]
High blood pressure DISY2OHH Strong Biomarker [18]
Influenza DIS3PNU3 Strong Genetic Variation [19]
leukaemia DISS7D1V Strong Genetic Variation [20]
Leukemia DISNAKFL Strong Genetic Variation [20]
Lung cancer DISCM4YA Strong Biomarker [21]
Lung carcinoma DISTR26C Strong Biomarker [21]
Lung neoplasm DISVARNB Strong Biomarker [22]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [21]
Osteoporosis DISF2JE0 Strong Biomarker [23]
Psoriasis DIS59VMN Strong Altered Expression [8]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [12]
Sjogren syndrome DISUBX7H Strong Altered Expression [24]
Systemic lupus erythematosus DISI1SZ7 Strong Altered Expression [25]
Vitamin B12 deficiency DIS91UJ1 Strong Altered Expression [26]
Tuberculosis DIS2YIMD Disputed Biomarker [27]
Breast cancer DIS7DPX1 Limited Biomarker [5]
Breast carcinoma DIS2UE88 Limited Biomarker [5]
Cervical cancer DISFSHPF Limited Biomarker [28]
Cervical carcinoma DIST4S00 Limited Biomarker [28]
Coronary heart disease DIS5OIP1 Limited Biomarker [15]
Gastric cancer DISXGOUK Limited Altered Expression [29]
Lung squamous cell carcinoma DISXPIBD Limited Biomarker [22]
Parkinson disease DISQVHKL Limited Biomarker [30]
Stomach cancer DISKIJSX Limited Altered Expression [29]
Type-1 diabetes DIS7HLUB Limited Biomarker [31]
Wilms tumor DISB6T16 Limited Biomarker [32]
------------------------------------------------------------------------------------
⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Platelet basic protein (PPBP). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Platelet basic protein (PPBP). [46]
------------------------------------------------------------------------------------
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Platelet basic protein (PPBP). [34]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Platelet basic protein (PPBP). [35]
Marinol DM70IK5 Approved Marinol increases the expression of Platelet basic protein (PPBP). [36]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Platelet basic protein (PPBP). [37]
Cocaine DMSOX7I Approved Cocaine increases the expression of Platelet basic protein (PPBP). [38]
Sertraline DM0FB1J Approved Sertraline decreases the expression of Platelet basic protein (PPBP). [39]
Amlodipine DMBDAZV Approved Amlodipine decreases the expression of Platelet basic protein (PPBP). [18]
Paroxetine DM5PVQE Approved Paroxetine decreases the expression of Platelet basic protein (PPBP). [42]
Nortriptyline DM4KDYJ Approved Nortriptyline affects the expression of Platelet basic protein (PPBP). [42]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Platelet basic protein (PPBP). [43]
Verapamil DMA7PEW Phase 2/3 Trial Verapamil decreases the expression of Platelet basic protein (PPBP). [44]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Platelet basic protein (PPBP). [45]
Eugenol DM7US1H Patented Eugenol increases the expression of Platelet basic protein (PPBP). [6]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Platelet basic protein (PPBP). [48]
cinnamaldehyde DMZDUXG Investigative cinnamaldehyde increases the expression of Platelet basic protein (PPBP). [6]
Beta-D-Glucose DM5IHYP Investigative Beta-D-Glucose increases the expression of Platelet basic protein (PPBP). [45]
------------------------------------------------------------------------------------
⏷ Show the Full List of 16 Drug(s)
2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ardeparin DMYRX8B Approved Ardeparin increases the secretion of Platelet basic protein (PPBP). [40]
adenosine diphosphate DMFUHKP Investigative adenosine diphosphate increases the secretion of Platelet basic protein (PPBP). [49]
------------------------------------------------------------------------------------

References

1 Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis.Ann Rheum Dis. 2016 Apr;75(4):763-71. doi: 10.1136/annrheumdis-2014-206921. Epub 2015 Apr 9.
2 PPBP and DEFA1/DEFA3 genes in hyperlipidaemia as feasible synergistic inflammatory biomarkers for coronary heart disease.Lipids Health Dis. 2017 Apr 19;16(1):80. doi: 10.1186/s12944-017-0471-0.
3 Platelet P-selectin and platelet mass, volume and component in sickle cell disease: relationship to genotype.Thromb Res. 2006;117(6):623-9. doi: 10.1016/j.thromres.2005.05.010. Epub 2005 Jul 27.
4 Increased levels of neutrophil-activating peptide-2 in acute coronary syndromes: possible role of platelet-mediated vascular inflammation.J Am Coll Cardiol. 2006 Oct 17;48(8):1591-9. doi: 10.1016/j.jacc.2006.06.060. Epub 2006 Sep 27.
5 CXCL7 promotes proliferation and invasion of cholangiocarcinoma cells.Oncol Rep. 2017 Feb;37(2):1114-1122. doi: 10.3892/or.2016.5312. Epub 2016 Dec 12.
6 Evaluation of selected biomarkers for the detection of chemical sensitization in human skin: a comparative study applying THP-1, MUTZ-3 and primary dendritic cells in culture. Toxicol In Vitro. 2013 Sep;27(6):1659-69. doi: 10.1016/j.tiv.2013.04.009. Epub 2013 Apr 26.
7 Elevated levels of the neutrophil chemoattractant pro-platelet basic protein in macrophages from individuals with chronic and allergic aspergillosis.J Infect Dis. 2015 Feb 15;211(4):651-60. doi: 10.1093/infdis/jiu490. Epub 2014 Sep 5.
8 Elevated platelet activation in patients with atopic dermatitis and psoriasis: increased plasma levels of beta-thromboglobulin and platelet factor 4.Allergol Int. 2008 Dec;57(4):391-6. doi: 10.2332/allergolint.O-08-537. Epub 2008 Dec 1.
9 Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of 'Trigger' and 'Substrate' Differences.Cell Physiol Biochem. 2018;47(3):1299-1309. doi: 10.1159/000490225. Epub 2018 Jun 15.
10 Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer.Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10848-53. doi: 10.1073/pnas.96.19.10848.
11 -Thromboglobulin and incident cardiovascular disease risk: The Atherosclerosis Risk in Communities study.Thromb Res. 2017 Jul;155:116-120. doi: 10.1016/j.thromres.2017.05.016. Epub 2017 May 17.
12 Expression level of CXCL7 in peripheral blood cells is a potential biomarker for the diagnosis of renal cell carcinoma.Cancer Sci. 2017 Dec;108(12):2495-2502. doi: 10.1111/cas.13414. Epub 2017 Oct 25.
13 Overexpression of chemokine receptor CXCR2 and ligand CXCL7 in liver metastases from colon cancer is correlated to shorter disease-free and overall survival.Cancer Sci. 2015 Mar;106(3):262-9. doi: 10.1111/cas.12603. Epub 2015 Mar 5.
14 The density of Tbet+ tumor-infiltrating T lymphocytes reflects an effective and druggable preexisting adaptive antitumor immune response in colorectal cancer, irrespective of the microsatellite status.Oncoimmunology. 2019 Jan 19;8(4):e1562834. doi: 10.1080/2162402X.2018.1562834. eCollection 2019.
15 The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes.Saudi J Biol Sci. 2018 Nov;25(7):1263-1271. doi: 10.1016/j.sjbs.2016.10.015. Epub 2016 Oct 24.
16 Chemokines in depression in health and in inflammatory illness: a systematic review and meta-analysis.Mol Psychiatry. 2018 Jan;23(1):48-58. doi: 10.1038/mp.2017.205. Epub 2017 Nov 14.
17 Platelet Microparticles Mediate Glomerular Endothelial Injury in Early Diabetic Nephropathy.J Am Soc Nephrol. 2018 Nov;29(11):2671-2695. doi: 10.1681/ASN.2018040368. Epub 2018 Oct 19.
18 Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy. Ann Med. 2004;36(7):552-7. doi: 10.1080/07853890410017386.
19 Molecular diagnosis and characterization of a culture-negative mycotic aneurysm due to ST54 Haemophilus influenzae type b with PBP 3 alterations.J Infect Chemother. 2018 Jul;24(7):570-572. doi: 10.1016/j.jiac.2017.12.013. Epub 2018 Jan 17.
20 Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells.Proc Natl Acad Sci U S A. 1987 May;84(9):2868-71. doi: 10.1073/pnas.84.9.2868.
21 CTAPIII/CXCL7: a novel biomarker for early diagnosis of lung cancer.Cancer Med. 2018 Feb;7(2):325-335. doi: 10.1002/cam4.1292. Epub 2018 Jan 22.
22 Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents.Oncotarget. 2017 Mar 21;8(12):18885-18900. doi: 10.18632/oncotarget.13806.
23 Ubiquitin-dependent proteolysis of CXCL7 leads to posterior longitudinal ligament ossification.PLoS One. 2018 May 21;13(5):e0196204. doi: 10.1371/journal.pone.0196204. eCollection 2018.
24 Tissue-specific up-regulation of the proteasome subunit beta5i (LMP7) in Sjgren's syndrome.Arthritis Rheum. 2006 May;54(5):1501-8. doi: 10.1002/art.21782.
25 Elevated beta-thromboglobulin and mean platelet volume levels may show persistent platelet activation in systemic lupus erythematosus patients.Adv Clin Exp Med. 2018 Sep;27(9):1279-1283. doi: 10.17219/acem/74389.
26 Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels.Br J Haematol. 2009 Nov;147(3):386-91. doi: 10.1111/j.1365-2141.2009.07855.x. Epub 2009 Aug 17.
27 Non-chemotactic influence of CXCL7 on human phagocytes. Modulation of antimicrobial activity against L. pneumophila.Immunobiology. 2012 Apr;217(4):394-401. doi: 10.1016/j.imbio.2011.10.015. Epub 2011 Nov 3.
28 Connective tissue activating peptide III expression disappears progressively with increased dysplasia in human cervical epithelium.Gynecol Oncol. 2000 Oct;79(1):23-7. doi: 10.1006/gyno.2000.5915.
29 Identification of plasma RGS18 and PPBP mRNAs as potential biomarkers for gastric cancer using transcriptome arrays.Oncol Lett. 2019 Jan;17(1):247-255. doi: 10.3892/ol.2018.9608. Epub 2018 Oct 23.
30 Peripheral assessment of the genes AQP4, PBP and TH in patients with Parkinson's disease.Neurochem Res. 2012 Mar;37(3):512-5. doi: 10.1007/s11064-011-0637-5. Epub 2011 Nov 15.
31 Bioinformatics analysis of gene expression in peripheral blood mononuclear cells from children with type 1 diabetes in 3 periods.Exp Clin Endocrinol Diabetes. 2014 Sep;122(8):477-83. doi: 10.1055/s-0034-1372599. Epub 2014 May 16.
32 Functional characterization of human nucleosome assembly protein-2 (NAP1L4) suggests a role as a histone chaperone.Genomics. 1997 Sep 15;44(3):253-65. doi: 10.1006/geno.1997.4868.
33 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
34 Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood. Toxicol Appl Pharmacol. 2017 Apr 15;321:57-66. doi: 10.1016/j.taap.2017.02.019. Epub 2017 Feb 24.
35 Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
36 Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
37 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
38 Cocaine activates platelets and increases the formation of circulating platelet containing microaggregates in humans. Heart. 2000 Jun;83(6):688-95. doi: 10.1136/heart.83.6.688.
39 Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy. Circulation. 2003 Aug 26;108(8):939-44. doi: 10.1161/01.CIR.0000085163.21752.0A. Epub 2003 Aug 11.
40 Carotid endarterectomy in patients with heparin-induced platelet activation: comparative efficacy of aspirin and iloprost (ZK36374). J Vasc Surg. 1987 May;5(5):693-701.
41 Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy. Ann Med. 2004;36(7):552-7. doi: 10.1080/07853890410017386.
42 Evaluation of platelet activation in depressed patients with ischemic heart disease after paroxetine or nortriptyline treatment. J Clin Psychopharmacol. 2000 Apr;20(2):137-40. doi: 10.1097/00004714-200004000-00004.
43 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
44 [Unstable stenocardia: indicators of platelet activity and the effect of verapamil]. Biull Vsesoiuznogo Kardiol Nauchn Tsentra AMN SSSR. 1987;10(2):33-9.
45 Induction and antimicrobial activity of platelet basic protein derivatives in human monocytes. J Leukoc Biol. 2004 Nov;76(5):1010-8. doi: 10.1189/jlb.0404261. Epub 2004 Aug 17.
46 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
47 Evaluation of selected biomarkers for the detection of chemical sensitization in human skin: a comparative study applying THP-1, MUTZ-3 and primary dendritic cells in culture. Toxicol In Vitro. 2013 Sep;27(6):1659-69. doi: 10.1016/j.tiv.2013.04.009. Epub 2013 Apr 26.
48 Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.
49 The role of nanoparticle size in hemocompatibility. Toxicology. 2009 Apr 28;258(2-3):139-47. doi: 10.1016/j.tox.2009.01.015. Epub 2009 Jan 22.