Details of Drug Off-Target (DOT)

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

DOT Name Growth/differentiation factor 11 (GDF11)
Synonyms GDF-11; Bone morphogenetic protein 11; BMP-11
Gene Name GDF11
Related Disease
Aplastic anemia ( )
Acute myocardial infarction ( )
Alzheimer disease ( )
Anemia ( )
Anorexia nervosa cachexia ( )
Arrhythmia ( )
Arteriosclerosis ( )
Arthritis ( )
Atherosclerosis ( )
Breast cancer ( )
Carcinoma of esophagus ( )
Cardiac failure ( )
Cerebral infarction ( )
Chronic obstructive pulmonary disease ( )
Colitis ( )
Colorectal neoplasm ( )
Congestive heart failure ( )
Dermatitis ( )
Esophageal cancer ( )
Hepatocellular carcinoma ( )
Hypertrophic cardiomyopathy ( )
Kidney failure ( )
Metabolic disorder ( )
Neoplasm ( )
Neoplasm of esophagus ( )
Nephropathy ( )
Non-insulin dependent diabetes ( )
Primary myelofibrosis ( )
Pulmonary arterial hypertension ( )
Renal fibrosis ( )
Rheumatoid arthritis ( )
Stroke ( )
Triple negative breast cancer ( )
Ulcerative colitis ( )
Uveal Melanoma ( )
Vertebral hypersegmentation and orofacial anomalies ( )
Cardiovascular disease ( )
Myelodysplastic syndrome ( )
Pancreatic cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Liver cancer ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Myocardial infarction ( )
Obesity ( )
Osteoporosis ( )
Type-1/2 diabetes ( )
UniProt ID
GDF11_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5E4G; 5JHW; 5UHM; 6MAC; 7MRZ
Pfam ID
PF00019 ; PF00688
Sequence
MVLAAPLLLGFLLLALELRPRGEAAEGPAAAAAAAAAAAAAGVGGERSSRPAPSVAPEPD
GCPVCVWRQHSRELRLESIKSQILSKLRLKEAPNISREVVKQLLPKAPPLQQILDLHDFQ
GDALQPEDFLEEDEYHATTETVISMAQETDPAVQTDGSPLCCHFHFSPKVMFTKVLKAQL
WVYLRPVPRPATVYLQILRLKPLTGEGTAGGGGGGRRHIRIRSLKIELHSRSGHWQSIDF
KQVLHSWFRQPQSNWGIEINAFDPSGTDLAVTSLGPGAEGLHPFMELRVLENTKRSRRNL
GLDCDEHSSESRCCRYPLTVDFEAFGWDWIIAPKRYKANYCSGQCEYMFMQKYPHTHLVQ
QANPRGSAGPCCTPTKMSPINMLYFNDKQQIIYGKIPGMVVDRCGCS
Function
Secreted signal that acts globally to regulate anterior/posterior axial patterning during development. May play critical roles in patterning both mesodermal and neural tissues. It is required for proper vertebral patterning and orofacial development. Signals through activin receptors type-2, ACVR2A and ACVR2B, and activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the phosphorylation of SMAD2 and SMAD3.
Tissue Specificity
In the embryo, strong expression is seen in the palatal epithelia, including the medial edge epithelial and midline epithelial seam of the palatal shelves. Less pronounced expression is also seen throughout the palatal shelf and tongue mesenchyme.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Aplastic anemia DISJRSC0 Definitive Biomarker [1]
Acute myocardial infarction DISE3HTG Strong Altered Expression [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Anemia DISTVL0C Strong Biomarker [1]
Anorexia nervosa cachexia DISFO5RQ Strong Biomarker [4]
Arrhythmia DISFF2NI Strong Biomarker [5]
Arteriosclerosis DISK5QGC Strong Biomarker [6]
Arthritis DIST1YEL Strong Biomarker [7]
Atherosclerosis DISMN9J3 Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Carcinoma of esophagus DISS6G4D Strong Biomarker [9]
Cardiac failure DISDC067 Strong Biomarker [10]
Cerebral infarction DISR1WNP Strong Biomarker [11]
Chronic obstructive pulmonary disease DISQCIRF Strong Biomarker [12]
Colitis DISAF7DD Strong Biomarker [6]
Colorectal neoplasm DISR1UCN Strong Altered Expression [13]
Congestive heart failure DIS32MEA Strong Biomarker [10]
Dermatitis DISY5SZC Strong Biomarker [14]
Esophageal cancer DISGB2VN Strong Biomarker [9]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [15]
Hypertrophic cardiomyopathy DISQG2AI Strong Altered Expression [16]
Kidney failure DISOVQ9P Strong Biomarker [17]
Metabolic disorder DIS71G5H Strong Biomarker [18]
Neoplasm DISZKGEW Strong Biomarker [15]
Neoplasm of esophagus DISOLKAQ Strong Biomarker [9]
Nephropathy DISXWP4P Strong Biomarker [17]
Non-insulin dependent diabetes DISK1O5Z Strong Altered Expression [19]
Primary myelofibrosis DIS6L0CN Strong Genetic Variation [20]
Pulmonary arterial hypertension DISP8ZX5 Strong Biomarker [21]
Renal fibrosis DISMHI3I Strong Altered Expression [17]
Rheumatoid arthritis DISTSB4J Strong Biomarker [7]
Stroke DISX6UHX Strong Biomarker [11]
Triple negative breast cancer DISAMG6N Strong Biomarker [8]
Ulcerative colitis DIS8K27O Strong Biomarker [6]
Uveal Melanoma DISA7ZGL Strong Altered Expression [22]
Vertebral hypersegmentation and orofacial anomalies DIS1CIPG Strong Autosomal dominant [23]
Cardiovascular disease DIS2IQDX moderate Altered Expression [24]
Myelodysplastic syndrome DISYHNUI moderate Genetic Variation [20]
Pancreatic cancer DISJC981 moderate Altered Expression [25]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Disputed Biomarker [26]
Liver cancer DISDE4BI Disputed Biomarker [26]
Advanced cancer DISAT1Z9 Limited Biomarker [27]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [28]
Myocardial infarction DIS655KI Limited Biomarker [5]
Obesity DIS47Y1K Limited Biomarker [19]
Osteoporosis DISF2JE0 Limited Biomarker [29]
Type-1/2 diabetes DISIUHAP Limited Biomarker [30]
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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
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Growth/differentiation factor 11 (GDF11). [31]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Growth/differentiation factor 11 (GDF11). [32]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Growth/differentiation factor 11 (GDF11). [33]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Growth/differentiation factor 11 (GDF11). [34]
Quercetin DM3NC4M Approved Quercetin increases the expression of Growth/differentiation factor 11 (GDF11). [35]
Marinol DM70IK5 Approved Marinol increases the expression of Growth/differentiation factor 11 (GDF11). [36]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Growth/differentiation factor 11 (GDF11). [37]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Growth/differentiation factor 11 (GDF11). [38]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Growth/differentiation factor 11 (GDF11). [39]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Growth/differentiation factor 11 (GDF11). [40]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Growth/differentiation factor 11 (GDF11). [41]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Growth/differentiation factor 11 (GDF11). [42]
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⏷ Show the Full List of 12 Drug(s)

References

1 GDF11 is increased in patients with aplastic anemia.Hematology. 2019 Dec;24(1):331-336. doi: 10.1080/16078454.2019.1574386.
2 TERT assists GDF11 to rejuvenate senescent VEGFR2(+)/CD133(+) cells in elderly patients with myocardial infarction.Lab Invest. 2019 Nov;99(11):1661-1688. doi: 10.1038/s41374-019-0290-1. Epub 2019 Jul 10.
3 GDF11 Rejuvenates Cerebrovascular Structure and Function in an Animal Model of Alzheimer's Disease.J Alzheimers Dis. 2018;62(2):807-819. doi: 10.3233/JAD-170474.
4 Relationship between serum level of growth differentiation factors 8, 11 and bone mineral density in girls with anorexia nervosa.Clin Endocrinol (Oxf). 2019 Jan;90(1):88-93. doi: 10.1111/cen.13871. Epub 2018 Oct 25.
5 Exogenous GDF11 attenuates non-canonical TGF- signaling to protect the heart from acute myocardial ischemia-reperfusion injury.Basic Res Cardiol. 2019 Mar 21;114(3):20. doi: 10.1007/s00395-019-0728-z.
6 Growth differentiation factor 11 ameliorates experimental colitis by inhibiting NLRP3 inflammasome activation.Am J Physiol Gastrointest Liver Physiol. 2018 Dec 1;315(6):G909-G920. doi: 10.1152/ajpgi.00159.2018. Epub 2018 Sep 6.
7 GDF11 antagonizes TNF--induced inflammation and protects against the development of inflammatory arthritis in mice.FASEB J. 2019 Mar;33(3):3317-3329. doi: 10.1096/fj.201801375RR. Epub 2018 Nov 8.
8 Tumor-Suppressor Inactivation of GDF11 Occurs by Precursor Sequestration in Triple-Negative Breast Cancer.Dev Cell. 2017 Nov 20;43(4):418-435.e13. doi: 10.1016/j.devcel.2017.10.027.
9 Effect of GDF11 on proliferation and apoptosis of esophageal cancer cells.Cell Mol Biol (Noisy-le-grand). 2018 Aug 30;64(11):80-84.
10 Growth differentiation factor 11 is involved in isoproterenolinduced heart failure.Mol Med Rep. 2019 May;19(5):4109-4118. doi: 10.3892/mmr.2019.10077. Epub 2019 Mar 22.
11 Growth differentiation factor 11 improves neurobehavioral recovery and stimulates angiogenesis in rats subjected to cerebral ischemia/reperfusion.Brain Res Bull. 2018 May;139:38-47. doi: 10.1016/j.brainresbull.2018.02.011. Epub 2018 Feb 9.
12 Reduced expression of growth differentiation factor 11 promoted the progression of chronic obstructive pulmonary disease by activating the AKT signaling pathway.Biomed Pharmacother. 2018 Jul;103:691-698. doi: 10.1016/j.biopha.2018.04.091. Epub 2018 Apr 24.
13 Clinical significance of growth differentiation factor 11 in colorectal cancer.Int J Oncol. 2007 Nov;31(5):1097-101.
14 GDF11 Antagonizes Psoriasis-like Skin Inflammation via Suppression of NF-B Signaling Pathway.Inflammation. 2019 Feb;42(1):319-330. doi: 10.1007/s10753-018-0895-3.
15 GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion.Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1540-1554. doi: 10.1016/j.bbadis.2019.03.003. Epub 2019 Mar 16.
16 GDF11 Attenuated ANG II-Induced Hypertrophic Cardiomyopathy and Expression of ANP, BNP and Beta-MHC Through Down- Regulating CCL11 in Mice.Curr Mol Med. 2018;18(10):661-671. doi: 10.2174/1566524019666190204112753.
17 GDF11 induces kidney fibrosis, renal cell epithelial-to-mesenchymal transition, and kidney dysfunction and failure.Surgery. 2018 Aug;164(2):262-273. doi: 10.1016/j.surg.2018.03.008. Epub 2018 May 3.
18 Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction-like phenotype in aged mice.Aging Cell. 2020 Jan;19(1):e13038. doi: 10.1111/acel.13038. Epub 2019 Oct 22.
19 Circulating GDF11 levels are decreased with age but are unchanged with obesity and type 2 diabetes.Aging (Albany NY). 2019 Mar 21;11(6):1733-1744. doi: 10.18632/aging.101865.
20 Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis.Blood. 2019 Feb 21;133(8):790-794. doi: 10.1182/blood-2018-11-876888. Epub 2019 Jan 2.
21 Growth Differentiation Factor 11 Promotes Abnormal Proliferation and Angiogenesis of Pulmonary Artery Endothelial Cells.Hypertension. 2018 Apr;71(4):729-741. doi: 10.1161/HYPERTENSIONAHA.117.10350. Epub 2018 Feb 20.
22 GDF11 upregulation independently predicts shorter overall-survival of uveal melanoma.PLoS One. 2019 Mar 18;14(3):e0214073. doi: 10.1371/journal.pone.0214073. eCollection 2019.
23 Mutations in GDF11 and the extracellular antagonist, Follistatin, as a likely cause of Mendelian forms of orofacial clefting in humans. Hum Mutat. 2019 Oct;40(10):1813-1825. doi: 10.1002/humu.23793. Epub 2019 Jun 18.
24 The versatility and paradox of GDF 11.Pharmacol Ther. 2017 Jul;175:28-34. doi: 10.1016/j.pharmthera.2017.02.032. Epub 2017 Feb 14.
25 GDF11 restrains tumor growth by promoting apoptosis in pancreatic cancer.Onco Targets Ther. 2018 Nov 27;11:8371-8379. doi: 10.2147/OTT.S181792. eCollection 2018.
26 GDF11/BMP11 as a novel tumor marker for liver cancer.Exp Ther Med. 2018 Apr;15(4):3495-3500. doi: 10.3892/etm.2018.5861. Epub 2018 Feb 12.
27 GDF11 Implications in Cancer Biology and Metabolism. Facts and Controversies.Front Oncol. 2019 Oct 15;9:1039. doi: 10.3389/fonc.2019.01039. eCollection 2019.
28 Cerebrospinal fluid from patients with amyotrophic lateral sclerosis inhibits sonic hedgehog function.PLoS One. 2017 Feb 7;12(2):e0171668. doi: 10.1371/journal.pone.0171668. eCollection 2017.
29 The GDF11-FTO-PPAR axis controls the shift of osteoporotic MSC fate to adipocyte and inhibits bone formation during osteoporosis.Biochim Biophys Acta Mol Basis Dis. 2018 Dec;1864(12):3644-3654. doi: 10.1016/j.bbadis.2018.09.015. Epub 2018 Sep 14.
30 GDF11 Improves Angiogenic Function of EPCs in Diabetic Limb Ischemia.Diabetes. 2018 Oct;67(10):2084-2095. doi: 10.2337/db17-1583. Epub 2018 Jul 19.
31 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.
32 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
33 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
34 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.
35 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
36 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
37 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
38 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
39 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
40 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
41 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
42 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.