Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV2S79X)

DOT Name	Myoblast determination protein 1 (MYOD1)
Synonyms	Class C basic helix-loop-helix protein 1; bHLHc1; Myogenic factor 3; Myf-3
Gene Name	MYOD1
Related Disease	Cardiac failure ( ) Congestive heart failure ( ) Adenoma ( ) Advanced cancer ( ) Alveolar soft part sarcoma ( ) Breast neoplasm ( ) Cardiovascular disease ( ) Colorectal adenoma ( ) Duchenne muscular dystrophy ( ) leukaemia ( ) Leukemia ( ) Malignant soft tissue neoplasm ( ) Muscular dystrophy ( ) Myopathy ( ) Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies ( ) Neoplasm ( ) Ovarian cancer ( ) Premature aging syndrome ( ) Prostate adenocarcinoma ( ) Retinoblastoma ( ) Sarcoma ( ) Turner syndrome ( ) Ulcerative colitis ( ) Breast carcinoma ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Fetal akinesia deformation sequence 1 ( ) High blood pressure ( ) Amyotrophic lateral sclerosis ( ) Breast cancer ( ) Cervical cancer ( ) Cervical carcinoma ( ) Colorectal carcinoma ( ) Colorectal neoplasm ( ) Congenital diaphragmatic hernia ( ) Lymphoid leukemia ( ) Metastatic malignant neoplasm ( ) Non-hodgkin lymphoma ( ) Obesity ( ) Wilms tumor ( )
UniProt ID	MYOD1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01586 ; PF00010 ; PF12232
Sequence	MELLSPPLRDVDLTAPDGSLCSFATTDDFYDDPCFDSPDLRFFEDLDPRLMHVGALLKPE EHSHFPAAVHPAPGAREDEHVRAPSGHHQAGRCLLWACKACKRKTTNADRRKAATMRERR RLSKVNEAFETLKRCTSSNPNQRLPKVEILRNAIRYIEGLQALLRDQDAAPPGAAAAFYA PGPLPPGRGGEHYSGDSDASSPRSNCSDGMMDYSGPPSGARRRNCYEGAYYNEAPSEPRP GKSAAVSSLDCLSSIVERISTESPAAPALLLADVPSESPPRRQEAAAPSEGESSGDPTQS PDAAPQCPAGANPNPIYQVL
Function	Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYF5 and MYOG, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Interacts with and is inhibited by the twist protein. This interaction probably involves the basic domains of both proteins.
KEGG Pathway	Spinocerebellar ataxia (hsa05017 )
Reactome Pathway	Myogenesis (R-HSA-525793 )

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Cardiac failure	DISDC067	Definitive	Therapeutic	[1]
Congestive heart failure	DIS32MEA	Definitive	Therapeutic	[1]
Adenoma	DIS78ZEV	Strong	Posttranslational Modification	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alveolar soft part sarcoma	DISLKJKZ	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Colorectal adenoma	DISTSVHM	Strong	Biomarker	[2]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[7]
leukaemia	DISS7D1V	Strong	Biomarker	[8]
Leukemia	DISNAKFL	Strong	Biomarker	[8]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Genetic Variation	[9]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[10]
Myopathy	DISOWG27	Strong	Biomarker	[11]
Myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies	DISMDGYH	Strong	Autosomal recessive	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[14]
Premature aging syndrome	DIS51AGT	Strong	Biomarker	[15]
Prostate adenocarcinoma	DISBZYU8	Strong	Posttranslational Modification	[16]
Retinoblastoma	DISVPNPB	Strong	Genetic Variation	[17]
Sarcoma	DISZDG3U	Strong	Genetic Variation	[9]
Turner syndrome	DIS2035C	Strong	Biomarker	[18]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[19]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[20]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[21]
Lung cancer	DISCM4YA	moderate	Biomarker	[21]
Lung carcinoma	DISTR26C	moderate	Biomarker	[21]
Fetal akinesia deformation sequence 1	DISKDI9L	Supportive	Autosomal recessive	[12]
High blood pressure	DISY2OHH	Disputed	Biomarker	[22]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Altered Expression	[23]
Breast cancer	DIS7DPX1	Limited	Biomarker	[20]
Cervical cancer	DISFSHPF	Limited	Posttranslational Modification	[24]
Cervical carcinoma	DIST4S00	Limited	Posttranslational Modification	[25]
Colorectal carcinoma	DIS5PYL0	Limited	Posttranslational Modification	[26]
Colorectal neoplasm	DISR1UCN	Limited	Posttranslational Modification	[26]
Congenital diaphragmatic hernia	DIS0IPVU	Limited	Biomarker	[27]
Lymphoid leukemia	DIS65TYQ	Limited	Posttranslational Modification	[28]
Metastatic malignant neoplasm	DIS86UK6	Limited	Genetic Variation	[29]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Posttranslational Modification	[28]
Obesity	DIS47Y1K	Limited	Biomarker	[30]
Wilms tumor	DISB6T16	Limited	Genetic Variation	[31]
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⏷ Show the Full List of 41 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Myoblast determination protein 1 (MYOD1).	[32]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Myoblast determination protein 1 (MYOD1).	[33]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Myoblast determination protein 1 (MYOD1).	[34]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Myoblast determination protein 1 (MYOD1).	[35]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Myoblast determination protein 1 (MYOD1).	[36]
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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 increases the methylation of Myoblast determination protein 1 (MYOD1).	[37]
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References

1	Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure.Growth Horm IGF Res. 2010 Apr;20(2):149-55. doi: 10.1016/j.ghir.2009.11.007. Epub 2010 Jan 8.
2	Hypermethylation of the Myf-3 gene in human colorectal cancer.Anticancer Res. 1997 Jan-Feb;17(1A):429-32.
3	The current landscape of rhabdomyosarcomas: an update.Virchows Arch. 2020 Jan;476(1):97-108. doi: 10.1007/s00428-019-02676-9. Epub 2019 Nov 6.
4	RT-PCR suggests human skeletal muscle origin of alveolar soft-part sarcoma.Oncology. 2000 May;58(4):319-23. doi: 10.1159/000012119.
5	The breast tumour-associated epithelial mucins and the peanut lectin binding urinary mucins are coded by a single highly polymorphic gene locus 'PUM'.Dis Markers. 1988 Jul-Sep;6(3):185-94.
6	Identification of diverse target RNAs that are functionally regulated by human Pumilio proteins.Nucleic Acids Res. 2018 Jan 9;46(1):362-386. doi: 10.1093/nar/gkx1120.
7	Modelling Duchenne muscular dystrophy in MYOD1-converted urine-derived cells treated with 3-deazaneplanocin A hydrochloride.Sci Rep. 2019 Mar 7;9(1):3807. doi: 10.1038/s41598-019-40421-z.
8	Direct Reprogramming of Fibroblasts Into Smooth Muscle-Like Cells With Defined Transcription Factors-Brief Report.Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2191-2197. doi: 10.1161/ATVBAHA.118.310870.
9	Beyond "Triton": Malignant Peripheral Nerve Sheath Tumors With Complete Heterologous Rhabdomyoblastic Differentiation Mimicking Spindle Cell Rhabdomyosarcoma.Am J Surg Pathol. 2019 Oct;43(10):1323-1330. doi: 10.1097/PAS.0000000000001290.
10	Dystrophinopathy carrier determination and detection of protein deficiencies in muscular dystrophy using lentiviral MyoD-forced myogenesis.Neuromuscul Disord. 2007 Apr;17(4):276-84. doi: 10.1016/j.nmd.2006.12.010. Epub 2007 Feb 15.
11	High efficiency myogenic conversion of human fibroblasts by adenoviral vector-mediated MyoD gene transfer. An alternative strategy for ex vivo gene therapy of primary myopathies.J Clin Invest. 1998 May 15;101(10):2119-28. doi: 10.1172/JCI1505.
12	Deficiency of the myogenic factor MyoD causes a perinatally lethal fetal akinesia. J Med Genet. 2016 Apr;53(4):264-9. doi: 10.1136/jmedgenet-2015-103620. Epub 2016 Jan 5.
13	Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum.Am J Surg Pathol. 2019 Jun;43(6):747-754. doi: 10.1097/PAS.0000000000001238.
14	Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis.Br J Cancer. 1997;75(3):396-402. doi: 10.1038/bjc.1997.64.
15	PUMILIO, but not RBMX, binding is required for regulation of genomic stability by noncoding RNA NORAD.Elife. 2019 Jul 25;8:e48625. doi: 10.7554/eLife.48625.
16	Role of glutathione-S-transferase P1 hypermethylation in molecular detection of prostate cancer.Genet Test Mol Biomarkers. 2011 Oct;15(10):667-70. doi: 10.1089/gtmb.2010.0262. Epub 2011 Jun 1.
17	Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration.Hum Mol Genet. 2006 Feb 15;15(4):637-51. doi: 10.1093/hmg/ddi479. Epub 2006 Jan 10.
18	A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome.Eur J Endocrinol. 2013 Jul 29;169(3):277-89. doi: 10.1530/EJE-13-0069. Print 2013 Sep.
19	DNA methylation of colon mucosa in ulcerative colitis patients: correlation with inflammatory status.Inflamm Bowel Dis. 2011 Sep;17(9):1955-65. doi: 10.1002/ibd.21573. Epub 2011 Jan 6.
20	Repression of ESR1 transcription by MYOD potentiates letrozole-resistance in ER-positive breast cancer cells.Biochem Biophys Res Commun. 2017 Oct 21;492(3):425-433. doi: 10.1016/j.bbrc.2017.08.082. Epub 2017 Aug 24.
21	Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1 in lung adenocarcinoma pleural effusions predicts survival in patients receiving platinum-based chemotherapy.Mol Med Rep. 2015 May;11(5):3523-32. doi: 10.3892/mmr.2014.3141. Epub 2014 Dec 30.
22	Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat.PLoS One. 2011;6(11):e27168. doi: 10.1371/journal.pone.0027168. Epub 2011 Nov 4.
23	Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis.Biomed Res Int. 2016;2016:5930621. doi: 10.1155/2016/5930621. Epub 2016 Apr 18.
24	DNA methylation in serum and tumors of cervical cancer patients.Clin Cancer Res. 2004 Jan 15;10(2):565-71. doi: 10.1158/1078-0432.ccr-0825-03.
25	Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.Clin Oncol (R Coll Radiol). 2015 Dec;27(12):720-7. doi: 10.1016/j.clon.2015.08.001. Epub 2015 Sep 4.
26	Hypermethylation of the MYOD1 gene is a novel prognostic factor in patients with colorectal cancer.Int J Mol Med. 2004 Mar;13(3):413-7.
27	The role of primary myogenic regulatory factors in the developing diaphragmatic muscle in the nitrofen-induced diaphragmatic hernia.Pediatr Surg Int. 2011 Jun;27(6):579-82. doi: 10.1007/s00383-010-2834-8.
28	The diagnositc significance of Myf-3 hypermethylation in malignant lymphoproliferative disorders.Leukemia. 2001 Apr;15(4):583-9. doi: 10.1038/sj.leu.2402080.
29	The expanding morphological and genetic spectrum of MYOD1-mutant spindle cell/sclerosing rhabdomyosarcomas: a clinicopathological and molecular comparison of mutated and non-mutated cases.Histopathology. 2019 May;74(6):933-943. doi: 10.1111/his.13819. Epub 2019 Apr 4.
30	The skeletal muscle Wnt pathway may modulate insulin resistance and muscle development in a diet-induced obese rat model.Obesity (Silver Spring). 2012 Aug;20(8):1577-84. doi: 10.1038/oby.2012.42. Epub 2012 Feb 21.
31	Methylation profile of the promoter CpG islands of 31 genes that may contribute to colorectal carcinogenesis.World J Gastroenterol. 2004 Dec 1;10(23):3441-54. doi: 10.3748/wjg.v10.i23.3441.
32	Oestradiol and SERM treatments influence oestrogen receptor coregulator gene expression in human skeletal muscle cells. Acta Physiol (Oxf). 2009 Nov;197(3):187-96. doi: 10.1111/j.1748-1716.2009.01997.x. Epub 2009 May 6.
33	Quercetin and Its Fermented Extract as a Potential Inhibitor of Bisphenol A-Exposed HT-29 Colon Cancer Cells' Viability. Int J Mol Sci. 2023 Mar 15;24(6):5604. doi: 10.3390/ijms24065604.
34	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.
35	Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
36	Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
37	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.