Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEVXGJ7)

DOT Name Growth/differentiation factor 10 (GDF10)
Synonyms GDF-10; Bone morphogenetic protein 3B; BMP-3B; Bone-inducing protein; BIP
Gene Name GDF10
Related Disease
Coronary heart disease ( )
Acute lymphocytic leukaemia ( )
Bipolar disorder ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cardiovascular disease ( )
Cerebral palsy ( )
Dystonia ( )
Fibrosarcoma ( )
Intellectual disability ( )
Lung neoplasm ( )
Mesothelioma ( )
Myocardial infarction ( )
Myocardial ischemia ( )
Neoplasm ( )
Neuralgia ( )
Non-small-cell lung cancer ( )
Obesity ( )
Oral cancer ( )
Osteosarcoma ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Retinoblastoma ( )
Squamous cell carcinoma ( )
Stroke ( )
Thyroid gland follicular carcinoma ( )
Triple negative breast cancer ( )
Advanced cancer ( )
Coronary atherosclerosis ( )
Invasive ductal breast carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Prediabetes syndrome ( )
Rectal carcinoma ( )
Type-1/2 diabetes ( )
UniProt ID
GDF10_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00019
Sequence
MAHVPARTSPGPGPQLLLLLLPLFLLLLRDVAGSHRAPAWSALPAAADGLQGDRDLQRHP
GDAAATLGPSAQDMVAVHMHRLYEKYSRQGARPGGGNTVRSFRARLEVVDQKAVYFFNLT
SMQDSEMILTATFHFYSEPPRWPRALEVLCKPRAKNASGRPLPLGPPTRQHLLFRSLSQN
TATQGLLRGAMALAPPPRGLWQAKDISPIVKAARRDGELLLSAQLDSEERDPGVPRPSPY
APYILVYANDLAISEPNSVAVTLQRYDPFPAGDPEPRAAPNNSADPRVRRAAQATGPLQD
NELPGLDERPPRAHAQHFHKHQLWPSPFRALKPRPGRKDRRKKGQEVFMAASQVLDFDEK
TMQKARRKQWDEPRVCSRRYLKVDFADIGWNEWIISPKSFDAYYCAGACEFPMPKIVRPS
NHATIQSIVRAVGIIPGIPEPCCVPDKMNSLGVLFLDENRNVVLKVYPNMSVDTCACR
Function
Growth factor involved in osteogenesis and adipogenesis. Plays an inhibitory role in the process of osteoblast differentiation via SMAD2/3 pathway. Plays an inhibitory role in the process of adipogenesis.
Tissue Specificity Expressed in femur, brain, lung, skeletal muscle, pancreas and testis.
KEGG Pathway
Cytokine-cytokine receptor interaction (hsa04060 )

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Coronary heart disease DIS5OIP1 Definitive Genetic Variation [1]
Acute lymphocytic leukaemia DISPX75S Strong Altered Expression [2]
Bipolar disorder DISAM7J2 Strong Altered Expression [3]
Bone osteosarcoma DIST1004 Strong Biomarker [4]
Breast cancer DIS7DPX1 Strong Biomarker [5]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Breast neoplasm DISNGJLM Strong Biomarker [5]
Cardiovascular disease DIS2IQDX Strong Biomarker [6]
Cerebral palsy DIS82ODL Strong Genetic Variation [7]
Dystonia DISJLFGW Strong Biomarker [8]
Fibrosarcoma DISWX7MU Strong Altered Expression [9]
Intellectual disability DISMBNXP Strong Genetic Variation [7]
Lung neoplasm DISVARNB Strong Altered Expression [10]
Mesothelioma DISKWK9M Strong Biomarker [11]
Myocardial infarction DIS655KI Strong Biomarker [12]
Myocardial ischemia DISFTVXF Strong Genetic Variation [13]
Neoplasm DISZKGEW Strong Biomarker [14]
Neuralgia DISWO58J Strong Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [16]
Obesity DIS47Y1K Strong Biomarker [17]
Oral cancer DISLD42D Strong Biomarker [18]
Osteosarcoma DISLQ7E2 Strong Biomarker [4]
Pancreatic cancer DISJC981 Strong Biomarker [19]
Prostate cancer DISF190Y Strong Biomarker [20]
Prostate carcinoma DISMJPLE Strong Biomarker [20]
Retinoblastoma DISVPNPB Strong Biomarker [20]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [18]
Stroke DISX6UHX Strong Biomarker [21]
Thyroid gland follicular carcinoma DISFK2QT Strong Biomarker [22]
Triple negative breast cancer DISAMG6N Strong Altered Expression [14]
Advanced cancer DISAT1Z9 moderate Altered Expression [23]
Coronary atherosclerosis DISKNDYU Limited Genetic Variation [1]
Invasive ductal breast carcinoma DIS43J58 Limited Altered Expression [24]
Lung cancer DISCM4YA Limited Genetic Variation [16]
Lung carcinoma DISTR26C Limited Genetic Variation [16]
Prediabetes syndrome DISH2I53 Limited Genetic Variation [25]
Rectal carcinoma DIS8FRR7 Limited Genetic Variation [26]
Type-1/2 diabetes DISIUHAP Limited Genetic Variation [25]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 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 10 (GDF10). [27]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Growth/differentiation factor 10 (GDF10). [28]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Growth/differentiation factor 10 (GDF10). [29]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Growth/differentiation factor 10 (GDF10). [30]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Growth/differentiation factor 10 (GDF10). [11]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Growth/differentiation factor 10 (GDF10). [32]
Testosterone Undecanoate DMZO10Y Approved Testosterone Undecanoate decreases the expression of Growth/differentiation factor 10 (GDF10). [33]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Growth/differentiation factor 10 (GDF10). [34]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Growth/differentiation factor 10 (GDF10). [35]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Growth/differentiation factor 10 (GDF10). [37]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Growth/differentiation factor 10 (GDF10). [38]
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⏷ Show the Full List of 11 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Growth/differentiation factor 10 (GDF10). [36]
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References

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3 Endoplasmic reticulum stress in bipolar disorder? - BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood.Psychoneuroendocrinology. 2018 Sep;95:113-119. doi: 10.1016/j.psyneuen.2018.05.029. Epub 2018 May 21.
4 Purification and partial identification of bone-inducing protein from a murine osteosarcoma.Biochem J. 1992 Jun 15;284 ( Pt 3)(Pt 3):847-54. doi: 10.1042/bj2840847.
5 Genetic variation in bone morphogenetic proteins and breast cancer risk in hispanic and non-hispanic white women: The breast cancer health disparities study.Int J Cancer. 2013 Jun 15;132(12):2928-39. doi: 10.1002/ijc.27960. Epub 2012 Dec 13.
6 Candidate gene polymorphism in cardiovascular disease: the BIP cohort.Isr Med Assoc J. 2006 Feb;8(2):103-5.
7 Bone Morphogenetic Protein (BMP)-3b Gene Depletion Causes High Mortality in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy.Front Neurol. 2018 Jun 5;9:397. doi: 10.3389/fneur.2018.00397. eCollection 2018.
8 A pilot trial of square biphasic pulse deep brain stimulation for dystonia: The BIP dystonia study.Mov Disord. 2017 Apr;32(4):615-618. doi: 10.1002/mds.26906. Epub 2017 Feb 13.
9 Use of the stress-inducible grp78/BiP promoter in targeting high level gene expression in fibrosarcoma in vivo.Cancer Res. 1995 Apr 15;55(8):1660-3.
10 Bone morphogenetic protein 3B silencing in non-small-cell lung cancer.Oncogene. 2004 Apr 29;23(20):3521-9. doi: 10.1038/sj.onc.1207441.
11 The aberrant promoter methylation of BMP3b and BMP6 in malignant pleural mesotheliomas. Oncol Rep. 2008 Nov;20(5):1265-8.
12 Over-expression of calpastatin attenuates myocardial injury following myocardial infarction by inhibiting endoplasmic reticulum stress.J Thorac Dis. 2018 Sep;10(9):5283-5297. doi: 10.21037/jtd.2018.08.133.
13 Association between epitopes detected by monoclonal antibody BIP-45 and the XbaI polymorphism of apolipoprotein B.Clin Genet. 1988 Mar;33(3):181-8. doi: 10.1111/j.1399-0004.1988.tb03435.x.
14 GDF10 inhibits proliferation and epithelial-mesenchymal transition in triple-negative breast cancer via upregulation of Smad7.Aging (Albany NY). 2019 May 31;11(10):3298-3314. doi: 10.18632/aging.101983.
15 Decrease of growth and differentiation factor 10 contributes to neuropathic pain through N-methyl-D-aspartate receptor activation.Neuroreport. 2017 May 24;28(8):444-450. doi: 10.1097/WNR.0000000000000785.
16 Interaction between the bone morphogenetic proteins and Ras/MAP-kinase signalling pathways in lung cancer.Br J Cancer. 2005 Oct 17;93(8):949-52. doi: 10.1038/sj.bjc.6602790.
17 Overexpression of bone morphogenetic protein-3b (BMP-3b) in adipose tissues protects against high-fat diet-induced obesity.Int J Obes (Lond). 2017 Apr;41(4):483-488. doi: 10.1038/ijo.2017.15. Epub 2017 Jan 20.
18 Loss of GDF10/BMP3b as a prognostic marker collaborates with TGFBR3 to enhance chemotherapy resistance and epithelial-mesenchymal transition in oral squamous cell carcinoma.Mol Carcinog. 2016 May;55(5):499-513. doi: 10.1002/mc.22297. Epub 2015 Mar 1.
19 Anti-pancreatic cancer activity of ONC212 involves the unfolded protein response (UPR) and is reduced by IGF1-R and GRP78/BIP.Oncotarget. 2017 Sep 12;8(47):81776-81793. doi: 10.18632/oncotarget.20819. eCollection 2017 Oct 10.
20 Osteoblast-Secreted Factors Mediate Dormancy of Metastatic Prostate Cancer in the Bone via Activation of the TGFRIII-p38MAPK-pS249/T252RB Pathway.Cancer Res. 2018 Jun 1;78(11):2911-2924. doi: 10.1158/0008-5472.CAN-17-1051. Epub 2018 Mar 7.
21 EPO promotes axonal sprouting via upregulating GDF10.Neurosci Lett. 2019 Oct 15;711:134412. doi: 10.1016/j.neulet.2019.134412. Epub 2019 Aug 2.
22 Caveolin-1 and caveolin-2,together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis.Cancer Res. 2003 Jun 1;63(11):2864-71.
23 HKH40A downregulates GRP78/BiP expression in cancer cells.Cell Death Dis. 2014 May 22;5(5):e1240. doi: 10.1038/cddis.2014.203.
24 Expression of fibrinogen E-fragment and fibrin E-fragment is inhibited in the human infiltrating ductal carcinoma of the breast: the two-dimensional electrophoresis and MALDI-TOF-mass spectrometry analyses.Int J Oncol. 2005 Nov;27(5):1425-31.
25 Common variants in PERK, JNK, BIP and XBP1 genes are associated with the risk of prediabetes or diabetes-related phenotypes in a Chinese population.Chin Med J (Engl). 2014;127(13):2438-44.
26 Genetic variation in bone morphogenetic protein and colon and rectal cancer.Int J Cancer. 2012 Feb 1;130(3):653-64. doi: 10.1002/ijc.26047. Epub 2011 Apr 27.
27 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
28 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.
29 Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
30 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
31 The aberrant promoter methylation of BMP3b and BMP6 in malignant pleural mesotheliomas. Oncol Rep. 2008 Nov;20(5):1265-8.
32 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
33 Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
34 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
35 Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
36 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.
37 The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
38 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.