Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU0YGC4)

DOT Name Fms-related tyrosine kinase 3 ligand (FLT3LG)
Synonyms Flt3 ligand; Flt3L; SL cytokine
Gene Name FLT3LG
Related Disease
Acute lymphocytic leukaemia ( )
Melanoma ( )
Pancreatic tumour ( )
Acute myelogenous leukaemia ( )
Adult glioblastoma ( )
Advanced cancer ( )
Arthritis ( )
Autoimmune disease ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiovascular disease ( )
Cervical cancer ( )
Cervical carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Hepatitis ( )
Hepatitis A virus infection ( )
Hepatocellular carcinoma ( )
Herpes simplex infection ( )
HIV infectious disease ( )
Immunodeficiency ( )
Inflammatory bowel disease ( )
leukaemia ( )
Malaria ( )
Myelodysplastic syndrome ( )
Non-hodgkin lymphoma ( )
Pancytopenia ( )
Pneumonia ( )
Pneumonitis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Pulmonary fibrosis ( )
Rheumatoid arthritis ( )
Brain neoplasm ( )
Glioblastoma multiforme ( )
Glioma ( )
Influenza ( )
Leukemia ( )
Lupus nephritis ( )
Neuroblastoma ( )
Systemic lupus erythematosus ( )
Asthma ( )
Bone osteosarcoma ( )
Osteosarcoma ( )
Small lymphocytic lymphoma ( )
UniProt ID
FLT3L_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1ETE; 3QS7; 3QS9; 7NBI; 7QDP; 7ZV9
Pfam ID
PF02947
Sequence
MTVLAPAWSPTTYLLLLLLLSSGLSGTQDCSFQHSPISSDFAVKIRELSDYLLQDYPVTV
ASNLQDEELCGGLWRLVLAQRWMERLKTVAGSKMQGLLERVNTEIHFVTKCAFQPPPSCL
RFVQTNISRLLQETSEQLVALKPWITRQNFSRCLELQCQPDSSTLPPPWSPRPLEATAPT
APQPPLLLLLLLPVGLLLLAAAWCLHWQRTRRRTPRPGEQVPPVPSPQDLLLVEH
Function Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
Ras sig.ling pathway (hsa04014 )
PI3K-Akt sig.ling pathway (hsa04151 )
Hematopoietic cell lineage (hsa04640 )
Pathways in cancer (hsa05200 )
Reactome Pathway
PIP3 activates AKT signaling (R-HSA-1257604 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
RAF/MAP kinase cascade (R-HSA-5673001 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
FLT3 Signaling (R-HSA-9607240 )
STAT5 Activation (R-HSA-9645135 )
Negative regulation of FLT3 (R-HSA-9706369 )
FLT3 signaling through SRC family kinases (R-HSA-9706374 )
FLT3 signaling by CBL mutants (R-HSA-9706377 )
PI3K Cascade (R-HSA-109704 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute lymphocytic leukaemia DISPX75S Definitive Biomarker [1]
Melanoma DIS1RRCY Definitive Biomarker [2]
Pancreatic tumour DIS3U0LK Definitive Biomarker [3]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [4]
Adult glioblastoma DISVP4LU Strong Biomarker [5]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Arthritis DIST1YEL Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Altered Expression [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Cardiovascular disease DIS2IQDX Strong Biomarker [9]
Cervical cancer DISFSHPF Strong Biomarker [10]
Cervical carcinoma DIST4S00 Strong Biomarker [10]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Biomarker [1]
Colon cancer DISVC52G Strong Biomarker [11]
Colon carcinoma DISJYKUO Strong Biomarker [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Hepatitis DISXXX35 Strong Altered Expression [13]
Hepatitis A virus infection DISUMFQV Strong Altered Expression [13]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [14]
Herpes simplex infection DISL1SAV Strong Altered Expression [15]
HIV infectious disease DISO97HC Strong Biomarker [16]
Immunodeficiency DIS093I0 Strong Biomarker [14]
Inflammatory bowel disease DISGN23E Strong Biomarker [17]
leukaemia DISS7D1V Strong Biomarker [18]
Malaria DISQ9Y50 Strong Biomarker [17]
Myelodysplastic syndrome DISYHNUI Strong Genetic Variation [19]
Non-hodgkin lymphoma DISS2Y8A Strong Altered Expression [20]
Pancytopenia DISVKEHV Strong Biomarker [21]
Pneumonia DIS8EF3M Strong Altered Expression [22]
Pneumonitis DIS88E0K Strong Altered Expression [22]
Prostate cancer DISF190Y Strong Altered Expression [23]
Prostate carcinoma DISMJPLE Strong Altered Expression [23]
Pulmonary fibrosis DISQKVLA Strong Biomarker [24]
Rheumatoid arthritis DISTSB4J Strong Biomarker [7]
Brain neoplasm DISY3EKS moderate Altered Expression [25]
Glioblastoma multiforme DISK8246 moderate Biomarker [5]
Glioma DIS5RPEH moderate Biomarker [26]
Influenza DIS3PNU3 moderate Biomarker [27]
Leukemia DISNAKFL moderate Biomarker [18]
Lupus nephritis DISCVGPZ moderate Altered Expression [28]
Neuroblastoma DISVZBI4 moderate Altered Expression [29]
Systemic lupus erythematosus DISI1SZ7 moderate Altered Expression [28]
Asthma DISW9QNS Limited Biomarker [30]
Bone osteosarcoma DIST1004 Limited Altered Expression [31]
Osteosarcoma DISLQ7E2 Limited Altered Expression [31]
Small lymphocytic lymphoma DIS30POX Limited Altered Expression [32]
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⏷ 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 increases the methylation of Fms-related tyrosine kinase 3 ligand (FLT3LG). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Fms-related tyrosine kinase 3 ligand (FLT3LG). [38]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [34]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [35]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [36]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol increases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [37]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [39]
AHPN DM8G6O4 Investigative AHPN decreases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [40]
Rutin DMEHRAJ Investigative Rutin decreases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [41]
CATECHIN DMY38SB Investigative CATECHIN decreases the expression of Fms-related tyrosine kinase 3 ligand (FLT3LG). [41]
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⏷ Show the Full List of 8 Drug(s)

References

1 Chemosensitivity is differentially regulated by the SDF-1/CXCR4 and SDF-1/CXCR7 axes in acute lymphoblastic leukemia with MLL gene rearrangements.Leuk Res. 2018 Dec;75:36-44. doi: 10.1016/j.leukres.2018.11.001. Epub 2018 Nov 3.
2 IL-12/23p40 overproduction by dendritic cells leads to an increased Th1 and Th17 polarization in a model of Yersinia enterocolitica-induced reactive arthritis in TNFRp55-/- mice.PLoS One. 2018 Mar 1;13(3):e0193573. doi: 10.1371/journal.pone.0193573. eCollection 2018.
3 Effect of Flt3 ligand gene transfer in experimental pancreatic cancer.Int J Colorectal Dis. 2007 Feb;22(2):215-23. doi: 10.1007/s00384-006-0118-5. Epub 2006 Mar 10.
4 Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia.Blood Adv. 2019 Oct 22;3(20):3052-3061. doi: 10.1182/bloodadvances.2019000197.
5 CD103(+) Cell Growth Factor Flt3L Enhances the Efficacy of Immune Checkpoint Blockades in Murine Glioblastoma Model.Oncol Res. 2018 Mar 5;26(2):173-182. doi: 10.3727/096504017X14841698396865. Epub 2017 Jan 20.
6 Development of a biodosimeter for radiation triage using novel blood protein biomarker panels in humans and non-human primates.Int J Radiat Biol. 2020 Jan;96(1):22-34. doi: 10.1080/09553002.2018.1532611. Epub 2019 Jan 3.
7 Fms-like tyrosine kinase 3 ligand controls formation of regulatory T cells in autoimmune arthritis.PLoS One. 2013;8(1):e54884. doi: 10.1371/journal.pone.0054884. Epub 2013 Jan 21.
8 Antitumor activity and immunotherapeutic properties of Flt3-ligand in a murine breast cancer model.Cancer Res. 1997 Aug 15;57(16):3511-6.
9 Dendritic cell-targeting DNA-based nasal adjuvants for protective mucosal immunity to Streptococcus pneumoniae.Microbiol Immunol. 2017 Jun;61(6):195-205. doi: 10.1111/1348-0421.12487.
10 A novel therapeutic vaccine composed of a rearranged human papillomavirus type 16 E6/E7 fusion protein and Fms-like tyrosine kinase-3 ligand induces CD8(+) T cell responses and antitumor effect.Vaccine. 2017 Nov 7;35(47):6459-6467. doi: 10.1016/j.vaccine.2017.09.003. Epub 2017 Oct 10.
11 Enhancement of anti-tumor effect of plasmid DNA-carrying MUC1 by the adjuvanticity of FLT3L in mouse model.Immunopharmacol Immunotoxicol. 2018 Aug;40(4):353-357. doi: 10.1080/08923973.2018.1498099. Epub 2018 Aug 15.
12 Fms-like tyrosine kinase 3 receptor ligand (Flt3L)-based vaccination administered with an adenoviral vector prevents tumor growth of colorectal cancer in a BALB/c mouse model.J Cancer Res Clin Oncol. 2013 Dec;139(12):2097-110. doi: 10.1007/s00432-013-1532-z. Epub 2013 Oct 10.
13 Ratios of T-helper 2 Cells to T-helper 1 Cells and Cytokine Levels in Patients with Hepatitis B.Chin Med J (Engl). 2017 Aug 5;130(15):1810-1815. doi: 10.4103/0366-6999.211541.
14 An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.Radiat Res. 2014 Aug;182(2):201-10. doi: 10.1667/RR13617.1. Epub 2014 Jul 3.
15 A novel bicistronic high-capacity gutless adenovirus vector that drives constitutive expression of herpes simplex virus type 1 thymidine kinase and tet-inducible expression of Flt3L for glioma therapeutics.J Virol. 2010 Jun;84(12):6007-17. doi: 10.1128/JVI.00398-10. Epub 2010 Apr 7.
16 Flt3L-Mediated Expansion of Plasmacytoid Dendritic Cells Suppresses HIV Infection in Humanized Mice.Cell Rep. 2019 Nov 26;29(9):2770-2782.e5. doi: 10.1016/j.celrep.2019.10.094.
17 Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo.Sci Rep. 2018 Jan 9;8(1):154. doi: 10.1038/s41598-017-18283-0.
18 Myeloid leukemia development in c-Cbl RING finger mutant mice is dependent on FLT3 signaling.Cancer Cell. 2010 Oct 19;18(4):341-52. doi: 10.1016/j.ccr.2010.09.008.
19 Haematopoietic and immune defects associated with GATA2 mutation.Br J Haematol. 2015 Apr;169(2):173-87. doi: 10.1111/bjh.13317. Epub 2015 Feb 23.
20 Interleukin 8 and Flt3 ligand as markers of advanced disease in primary gastrointestinal non-Hodgkin's lymphoma.Oncol Rep. 2002 May-Jun;9(3):525-7.
21 Kinetics of plasma FLT3 ligand concentration in hematopoietic stem cell transplanted patients.Leuk Lymphoma. 2006 Jan;47(1):77-80. doi: 10.1080/10428190500175122.
22 Classical dendritic cells regulate acute lung inflammation and injury in mice with lipopolysaccharideinduced acute respiratory distress syndrome.Int J Mol Med. 2019 Aug;44(2):617-629. doi: 10.3892/ijmm.2019.4208. Epub 2019 May 23.
23 Antigen-specific IgG elicited in subjects with prostate cancer treated with flt3 ligand.J Immunother. 2005 May-Jun;28(3):268-75. doi: 10.1097/01.cji.0000158853.15664.0c.
24 The FMS-like tyrosine kinase-3 ligand/lung dendritic cell axis contributes to regulation of pulmonary fibrosis.Thorax. 2019 Oct;74(10):947-957. doi: 10.1136/thoraxjnl-2018-212603. Epub 2019 May 10.
25 Preclinical Efficacy and Safety Profile of Allometrically Scaled Doses of Doxycycline Used to Turn "On" Therapeutic Transgene Expression from High-Capacity Adenoviral Vectors in a Glioma Model.Hum Gene Ther Methods. 2016 Jun;27(3):98-111. doi: 10.1089/hgtb.2015.168. Epub 2016 Apr 28.
26 Safety profile, efficacy, and biodistribution of a bicistronic high-capacity adenovirus vector encoding a combined immunostimulation and cytotoxic gene therapy as a prelude to a phase I clinical trial for glioblastoma.Toxicol Appl Pharmacol. 2013 May 1;268(3):318-30. doi: 10.1016/j.taap.2013.02.001. Epub 2013 Feb 9.
27 Alteration of Flt3-Ligand-dependent de novo generation of conventional dendritic cells during influenza infection contributes to respiratory bacterial superinfection.PLoS Pathog. 2018 Oct 29;14(10):e1007360. doi: 10.1371/journal.ppat.1007360. eCollection 2018 Oct.
28 Mesenchymal stem cell therapy induces FLT3L and CD1c(+) dendritic cells in systemic lupus erythematosus patients.Nat Commun. 2019 Jun 7;10(1):2498. doi: 10.1038/s41467-019-10491-8.
29 Flt-3 and its ligand are expressed in neural crest-derived tumors and promote survival and proliferation of their cell lines.Lab Invest. 2001 Jul;81(7):1025-37. doi: 10.1038/labinvest.3780314.
30 Flt3 ligand: a novel cytokine prevents allergic asthma in a mouse model.Int Immunopharmacol. 2001 Nov;1(12):2081-9. doi: 10.1016/s1567-5769(01)00122-9.
31 A novel prognostic model for osteosarcoma using circulating CXCL10 and FLT3LG.Cancer. 2017 Jan 1;123(1):144-154. doi: 10.1002/cncr.30272. Epub 2016 Aug 16.
32 Purine-rich box-1-mediated reduced expression of CD20 alters rituximab-induced lysis of chronic lymphocytic leukemia B cells.Cancer Res. 2008 Sep 15;68(18):7512-9. doi: 10.1158/0008-5472.CAN-07-6446.
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 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
35 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
36 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.
37 Analysis of gene expression induced by diethylstilbestrol (DES) in human primitive Mullerian duct cells using microarray. Cancer Lett. 2005 Apr 8;220(2):197-210.
38 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.
39 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
40 ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
41 Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.