Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9GC6TP)

• DOT Name: Granulocyte colony-stimulating factor (CSF3)
• Synonyms: G-CSF; Pluripoietin; Filgrastim; Lenograstim
• Gene Name: CSF3
• UniProt ID: CSF3_HUMAN
• PDB ID: 1CD9; 1GNC; 1PGR; 1RHG; 2D9Q; 5GW9; 5ZO6
• Pfam ID: PF16647
• Sequence:
  MAGPATQSPMKLMALQLLLWHSALWTVQEATPLGPASSLPQSFLLKCLEQVRKIQGDGAA
  LQEKLVSECATYKLCHPEELVLLGHSLGIPWAPLSSCPSQALQLAGCLSQLHSGLFLYQG
  LLQALEGISPELGPTLDTLQLDVADFATTIWQQMEELGMAPALQPTQGAMPAFASAFQRR
  AGGVLVASHLQSFLEVSYRVLRHLAQP
• Function: Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  IL-17 sig.ling pathway (hsa04657)
  Malaria (hsa05144)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  Interleukin-10 signaling (R-HSA-6783783)
  Signaling by CSF3 (G-CSF) (R-HSA-9674555)
  Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462)
  Other interleukin signaling (R-HSA-449836)

Molecular Interaction Atlas (MIA) of This DOT

22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Granulocyte colony-stimulating factor (CSF3).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Granulocyte colony-stimulating factor (CSF3).	[5]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Granulocyte colony-stimulating factor (CSF3).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Granulocyte colony-stimulating factor (CSF3).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[8]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[9]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Granulocyte colony-stimulating factor (CSF3).	[10]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Granulocyte colony-stimulating factor (CSF3).	[11]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[12]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the activity of Granulocyte colony-stimulating factor (CSF3).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Granulocyte colony-stimulating factor (CSF3).	[15]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Granulocyte colony-stimulating factor (CSF3).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Granulocyte colony-stimulating factor (CSF3).	[18]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Granulocyte colony-stimulating factor (CSF3).	[19]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[20]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Granulocyte colony-stimulating factor (CSF3).	[21]
[3H]cAMP	DMZRQU7	Investigative	[3H]cAMP increases the expression of Granulocyte colony-stimulating factor (CSF3).	[16]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Pomalidomide	DMTGBAX	Approved	Pomalidomide increases the secretion of Granulocyte colony-stimulating factor (CSF3).	[14]

References

• [1] Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes. BMC Immunol. 2006 Nov 21;7:27. doi: 10.1186/1471-2172-7-27.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [5] Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
• [6] Glucocorticoids inhibit cell death in ovarian cancer and up-regulate caspase inhibitor cIAP2. Clin Cancer Res. 2005 Sep 1;11(17):6325-32. doi: 10.1158/1078-0432.CCR-05-0182.
• [7] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [8] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [9] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [10] Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC). Front Microbiol. 2015 Dec 22;6:1452. doi: 10.3389/fmicb.2015.01452. eCollection 2015.
• [11] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [12] Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma. Br J Cancer. 2010 Jun 29;103(1):52-60.
• [13] Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo. Int J Cancer. 2007 Oct 15;121(8):1697-704. doi: 10.1002/ijc.22867.
• [14] Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
• [15] Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung. Toxicol Appl Pharmacol. 2017 Jun 1;324:1-11. doi: 10.1016/j.taap.2017.03.019. Epub 2017 Mar 27.
• [16] Human fibroblasts (KMST-6/RAS cell line) transformed with 60Co gamma-rays and c-Ha-ras oncogene produce a large amount of granulocyte colony-stimulating factor (G-CSF); production is enhanced by cAMP, theophylline, and butyrate. Cell Struct Funct. 1995 Feb;20(1):41-5. doi: 10.1247/csf.20.41.
• [17] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [18] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [19] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [20] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
• [21] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.