Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXN2WXS)

• DOT Name: Myosin-10 (MYH10)
• Synonyms: Cellular myosin heavy chain, type B; Myosin heavy chain 10; Myosin heavy chain, non-muscle IIb; Non-muscle myosin heavy chain B; NMMHC-B; Non-muscle myosin heavy chain IIb; NMMHC II-b; NMMHC-IIB
• Gene Name: MYH10
• Related Disease:
  Acute myelogenous leukaemia
  Chronic myelomonocytic leukaemia
  Chronic myelomonocytic leukemia
  Inherited bleeding disorder, platelet-type
  Neoplasm
  Thrombocytopenia
  Aortic aneurysm
  Autism spectrum disorder
  Glioma
  Immune system disorder
  Inflammatory bowel disease
  Lung squamous cell carcinoma
  Pulmonary disease
  Pulmonary emphysema
  Breast cancer
  Breast carcinoma
  Focal segmental glomerulosclerosis
  Melanoma
• UniProt ID: MYH10_HUMAN
• PDB ID: 4PD3
• Pfam ID: PF00612 ; PF00063 ; PF02736 ; PF01576
• Sequence:
  MAQRTGLEDPERYLFVDRAVIYNPATQADWTAKKLVWIPSERHGFEAASIKEERGDEVMV
  ELAENGKKAMVNKDDIQKMNPPKFSKVEDMAELTCLNEASVLHNLKDRYYSGLIYTYSGL
  FCVVINPYKNLPIYSENIIEMYRGKKRHEMPPHIYAISESAYRCMLQDREDQSILCTGES
  GAGKTENTKKVIQYLAHVASSHKGRKDHNIPGELERQLLQANPILESFGNAKTVKNDNSS
  RFGKFIRINFDVTGYIVGANIETYLLEKSRAVRQAKDERTFHIFYQLLSGAGEHLKSDLL
  LEGFNNYRFLSNGYIPIPGQQDKDNFQETMEAMHIMGFSHEEILSMLKVVSSVLQFGNIS
  FKKERNTDQASMPENTVAQKLCHLLGMNVMEFTRAILTPRIKVGRDYVQKAQTKEQADFA
  VEALAKATYERLFRWLVHRINKALDRTKRQGASFIGILDIAGFEIFELNSFEQLCINYTN
  EKLQQLFNHTMFILEQEEYQREGIEWNFIDFGLDLQPCIDLIERPANPPGVLALLDEECW
  FPKATDKTFVEKLVQEQGSHSKFQKPRQLKDKADFCIIHYAGKVDYKADEWLMKNMDPLN
  DNVATLLHQSSDRFVAELWKDVDRIVGLDQVTGMTETAFGSAYKTKKGMFRTVGQLYKES
  LTKLMATLRNTNPNFVRCIIPNHEKRAGKLDPHLVLDQLRCNGVLEGIRICRQGFPNRIV
  FQEFRQRYEILTPNAIPKGFMDGKQACERMIRALELDPNLYRIGQSKIFFRAGVLAHLEE
  ERDLKITDIIIFFQAVCRGYLARKAFAKKQQQLSALKVLQRNCAAYLKLRHWQWWRVFTK
  VKPLLQVTRQEEELQAKDEELLKVKEKQTKVEGELEEMERKHQQLLEEKNILAEQLQAET
  ELFAEAEEMRARLAAKKQELEEILHDLESRVEEEEERNQILQNEKKKMQAHIQDLEEQLD
  EEEGARQKLQLEKVTAEAKIKKMEEEILLLEDQNSKFIKEKKLMEDRIAECSSQLAEEEE
  KAKNLAKIRNKQEVMISDLEERLKKEEKTRQELEKAKRKLDGETTDLQDQIAELQAQIDE
  LKLQLAKKEEELQGALARGDDETLHKNNALKVVRELQAQIAELQEDFESEKASRNKAEKQ
  KRDLSEELEALKTELEDTLDTTAAQQELRTKREQEVAELKKALEEETKNHEAQIQDMRQR
  HATALEELSEQLEQAKRFKANLEKNKQGLETDNKELACEVKVLQQVKAESEHKRKKLDAQ
  VQELHAKVSEGDRLRVELAEKASKLQNELDNVSTLLEEAEKKGIKFAKDAASLESQLQDT
  QELLQEETRQKLNLSSRIRQLEEEKNSLQEQQEEEEEARKNLEKQVLALQSQLADTKKKV
  DDDLGTIESLEEAKKKLLKDAEALSQRLEEKALAYDKLEKTKNRLQQELDDLTVDLDHQR
  QVASNLEKKQKKFDQLLAEEKSISARYAEERDRAEAEAREKETKALSLARALEEALEAKE
  EFERQNKQLRADMEDLMSSKDDVGKNVHELEKSKRALEQQVEEMRTQLEELEDELQATED
  AKLRLEVNMQAMKAQFERDLQTRDEQNEEKKRLLIKQVRELEAELEDERKQRALAVASKK
  KMEIDLKDLEAQIEAANKARDEVIKQLRKLQAQMKDYQRELEEARASRDEIFAQSKESEK
  KLKSLEAEILQLQEELASSERARRHAEQERDELADEITNSASGKSALLDEKRRLEARIAQ
  LEEELEEEQSNMELLNDRFRKTTLQVDTLNAELAAERSAAQKSDNARQQLERQNKELKAK
  LQELEGAVKSKFKATISALEAKIGQLEEQLEQEAKERAAANKLVRRTEKKLKEIFMQVED
  ERRHADQYKEQMEKANARMKQLKRQLEEAEEEATRANASRRKLQRELDDATEANEGLSRE
  VSTLKNRLRRGGPISFSSSRSGRRQLHLEGASLELSDDDTESKTSDVNETQPPQSE
• Function: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the central part but not the margins of spreading cells), and lamellipodial extension; this function is mechanically antagonized by MYH9.
• Tissue Specificity: Isoform 1 is expressed in cerebellum and spinal chord. Isoform 2 is expressed in cerebrum and retina. Isoform 3 is expressed in the cerebrum and to a much lower extent in cerebellum.
• KEGG Pathway:
  Vascular smooth muscle contraction (hsa04270)
  Tight junction (hsa04530)
  Regulation of actin cytoskeleton (hsa04810)
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
  Pathogenic Escherichia coli infection (hsa05130)
• Reactome Pathway:
  Sema4D induced cell migration and growth-cone collapse (R-HSA-416572)
  RHO GTPases activate PKNs (R-HSA-5625740)
  RHO GTPases activate CIT (R-HSA-5625900)
  RHO GTPases Activate ROCKs (R-HSA-5627117)
  RHO GTPases activate PAKs (R-HSA-5627123)
  EPHA-mediated growth cone collapse (R-HSA-3928663)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Chronic myelomonocytic leukaemia	DISDN5P7	Definitive	Biomarker	[1]
Chronic myelomonocytic leukemia	DISIL8UR	Definitive	Biomarker	[1]
Inherited bleeding disorder, platelet-type	DISIUNXT	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Thrombocytopenia	DISU61YW	Definitive	Biomarker	[1]
Aortic aneurysm	DISQ5KRA	Strong	Biomarker	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Immune system disorder	DISAEGPH	Strong	Biomarker	[5]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[6]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[7]
Pulmonary disease	DIS6060I	moderate	Biomarker	[8]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[8]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[9]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[9]
Focal segmental glomerulosclerosis	DISJNHH0	Limited	Biomarker	[10]
Melanoma	DIS1RRCY	Limited	Biomarker	[11]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Myosin-10 (MYH10) increases the response to substance of Arsenic.	[35]
Cyclophosphamide	DM4O2Z7	Approved	Myosin-10 (MYH10) affects the response to substance of Cyclophosphamide.	[36]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Myosin-10 (MYH10).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Myosin-10 (MYH10).	[31]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Myosin-10 (MYH10).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Myosin-10 (MYH10).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myosin-10 (MYH10).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Myosin-10 (MYH10).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Myosin-10 (MYH10).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myosin-10 (MYH10).	[17]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Myosin-10 (MYH10).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myosin-10 (MYH10).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Myosin-10 (MYH10).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Myosin-10 (MYH10).	[22]
Marinol	DM70IK5	Approved	Marinol increases the expression of Myosin-10 (MYH10).	[23]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Myosin-10 (MYH10).	[24]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Myosin-10 (MYH10).	[25]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Myosin-10 (MYH10).	[26]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Myosin-10 (MYH10).	[27]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the expression of Myosin-10 (MYH10).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Myosin-10 (MYH10).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Myosin-10 (MYH10).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myosin-10 (MYH10).	[30]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Myosin-10 (MYH10).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myosin-10 (MYH10).	[33]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Myosin-10 (MYH10).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the localization of Myosin-10 (MYH10).	[21]

References

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• [3] The Contribution of Mosaic Variants to Autism Spectrum Disorder.PLoS Genet. 2016 Sep 15;12(9):e1006245. doi: 10.1371/journal.pgen.1006245. eCollection 2016 Sep.
• [4] Myosin Heavy Chain 10 (MYH10) Gene Silencing Reduces Cell Migration and Invasion in the Glioma Cell Lines U251, T98G, and SHG44 by Inhibiting the Wnt/-Catenin Pathway.Med Sci Monit. 2018 Dec 15;24:9110-9119. doi: 10.12659/MSM.911523.
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• [18] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [19] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [20] Grouping of histone deacetylase inhibitors and other toxicants disturbing neural crest migration by transcriptional profiling. Neurotoxicology. 2015 Sep;50:56-70.
• [21] DNA double-strand breaks and Aurora B mislocalization induced by exposure of early mitotic cells to H(2)O(2) appear to increase chromatin bridges and resultant cytokinesis failure. Free Radic Biol Med. 2017 Jul;108:129-145. doi: 10.1016/j.freeradbiomed.2017.03.025. Epub 2017 Mar 24.
• [22] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [23] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
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• [26] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [27] Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. Cardiovasc Res. 2005 Aug 1;67(2):333-41. doi: 10.1016/j.cardiores.2005.03.016. Epub 2005 Apr 21.
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