Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVNVWY3)

• DOT Name: Myosin-11 (MYH11)
• Synonyms: Myosin heavy chain 11; Myosin heavy chain, smooth muscle isoform; SMMHC
• Gene Name: MYH11
• Related Disease:
  Familial thoracic aortic aneurysm and aortic dissection
  High blood pressure
  Pneumonia
  Abdominal aortic aneurysm
  Acute lymphocytic leukaemia
  Acute megakaryoblastic leukemia
  Acute monocytic leukemia
  Acute undifferentiated leukemia
  Adenoma
  Advanced cancer
  Aortic aneurysm
  Aortic aneurysm, familial thoracic 4
  Aortic disorder
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Colorectal neoplasm
  Gastric cancer
  Hypospadias
  Leukopenia
  Megacystis-microcolon-intestinal hypoperistalsis syndrome 2
  Metastatic malignant neoplasm
  Myelodysplastic syndrome
  Myeloid leukaemia
  Non-small-cell lung cancer
  Patent ductus arteriosus
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Schizophrenia
  Wilms tumor
  Coronary heart disease
  Obsolete megacystis-microcolon-intestinal hypoperistalsis syndrome
  Trichohepatoenteric syndrome
  Acute leukaemia
  Asthma
  Childhood acute lymphoblastic leukemia
  Chromosomal disorder
  Colorectal carcinoma
  Megacystis-microcolon-intestinal hypoperistalsis syndrome
  Peutz-Jeghers syndrome
  Visceral myopathy 2
• UniProt ID: MYH11_HUMAN
• Pfam ID: PF00063 ; PF02736 ; PF01576
• Sequence:
  MAQKGQLSDDEKFLFVDKNFINSPVAQADWAAKRLVWVPSEKQGFEAASIKEEKGDEVVV
  ELVENGKKVTVGKDDIQKMNPPKFSKVEDMAELTCLNEASVLHNLRERYFSGLIYTYSGL
  FCVVVNPYKHLPIYSEKIVDMYKGKKRHEMPPHIYAIADTAYRSMLQDREDQSILCTGES
  GAGKTENTKKVIQYLAVVASSHKGKKDTSITGELEKQLLQANPILEAFGNAKTVKNDNSS
  RFGKFIRINFDVTGYIVGANIETYLLEKSRAIRQARDERTFHIFYYMIAGAKEKMRSDLL
  LEGFNNYTFLSNGFVPIPAAQDDEMFQETVEAMAIMGFSEEEQLSILKVVSSVLQLGNIV
  FKKERNTDQASMPDNTAAQKVCHLMGINVTDFTRSILTPRIKVGRDVVQKAQTKEQADFA
  VEALAKATYERLFRWILTRVNKALDKTHRQGASFLGILDIAGFEIFEVNSFEQLCINYTN
  EKLQQLFNHTMFILEQEEYQREGIEWNFIDFGLDLQPCIELIERPNNPPGVLALLDEECW
  FPKATDKSFVEKLCTEQGSHPKFQKPKQLKDKTEFSIIHYAGKVDYNASAWLTKNMDPLN
  DNVTSLLNASSDKFVADLWKDVDRIVGLDQMAKMTESSLPSASKTKKGMFRTVGQLYKEQ
  LGKLMTTLRNTTPNFVRCIIPNHEKRSGKLDAFLVLEQLRCNGVLEGIRICRQGFPNRIV
  FQEFRQRYEILAANAIPKGFMDGKQACILMIKALELDPNLYRIGQSKIFFRTGVLAHLEE
  ERDLKITDVIMAFQAMCRGYLARKAFAKRQQQLTAMKVIQRNCAAYLKLRNWQWWRLFTK
  VKPLLQVTRQEEEMQAKEDELQKTKERQQKAENELKELEQKHSQLTEEKNLLQEQLQAET
  ELYAEAEEMRVRLAAKKQELEEILHEMEARLEEEEDRGQQLQAERKKMAQQMLDLEEQLE
  EEEAARQKLQLEKVTAEAKIKKLEDEILVMDDQNNKLSKERKLLEERISDLTTNLAEEEE
  KAKNLTKLKNKHESMISELEVRLKKEEKSRQELEKLKRKLEGDASDFHEQIADLQAQIAE
  LKMQLAKKEEELQAALARLDDEIAQKNNALKKIRELEGHISDLQEDLDSERAARNKAEKQ
  KRDLGEELEALKTELEDTLDSTATQQELRAKREQEVTVLKKALDEETRSHEAQVQEMRQK
  HAQAVEELTEQLEQFKRAKANLDKNKQTLEKENADLAGELRVLGQAKQEVEHKKKKLEAQ
  VQELQSKCSDGERARAELNDKVHKLQNEVESVTGMLNEAEGKAIKLAKDVASLSSQLQDT
  QELLQEETRQKLNVSTKLRQLEEERNSLQDQLDEEMEAKQNLERHISTLNIQLSDSKKKL
  QDFASTVEALEEGKKRFQKEIENLTQQYEEKAAAYDKLEKTKNRLQQELDDLVVDLDNQR
  QLVSNLEKKQRKFDQLLAEEKNISSKYADERDRAEAEAREKETKALSLARALEEALEAKE
  ELERTNKMLKAEMEDLVSSKDDVGKNVHELEKSKRALETQMEEMKTQLEELEDELQATED
  AKLRLEVNMQALKGQFERDLQARDEQNEEKRRQLQRQLHEYETELEDERKQRALAAAAKK
  KLEGDLKDLELQADSAIKGREEAIKQLRKLQAQMKDFQRELEDARASRDEIFATAKENEK
  KAKSLEADLMQLQEDLAAAERARKQADLEKEELAEELASSLSGRNALQDEKRRLEARIAQ
  LEEELEEEQGNMEAMSDRVRKATQQAEQLSNELATERSTAQKNESARQQLERQNKELRSK
  LHEMEGAVKSKFKSTIAALEAKIAQLEEQVEQEAREKQAATKSLKQKDKKLKEILLQVED
  ERKMAEQYKEQAEKGNARVKQLKRQLEEAEEESQRINANRRKLQRELDEATESNEAMGRE
  VNALKSKLRRGNETSFVPSRRSGGRRVIENADGSEEETDTRDADFNGTKASE
• Function: Muscle contraction.
• Tissue Specificity: Smooth muscle; expressed in the umbilical artery, bladder, esophagus and trachea. Isoform 1 is mostly found in slowly contracting tonic muscles.
• 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)
  Smooth Muscle Contraction (R-HSA-445355)
  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

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial thoracic aortic aneurysm and aortic dissection	DIS069FB	Definitive	Autosomal dominant	[1]
High blood pressure	DISY2OHH	Definitive	Altered Expression	[2]
Pneumonia	DIS8EF3M	Definitive	Biomarker	[3]
Abdominal aortic aneurysm	DISD06OF	Strong	Altered Expression	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[4]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[5]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[6]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Altered Expression	[7]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Aortic aneurysm	DISQ5KRA	Strong	Biomarker	[10]
Aortic aneurysm, familial thoracic 4	DISLIFJ4	Strong	Autosomal dominant	[11]
Aortic disorder	DISKXISV	Strong	Genetic Variation	[12]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[13]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[13]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[14]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[14]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[15]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[16]
Hypospadias	DIS48CCP	Strong	Posttranslational Modification	[17]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[6]
Megacystis-microcolon-intestinal hypoperistalsis syndrome 2	DISB16W4	Strong	Autosomal recessive	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[19]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[20]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[22]
Patent ductus arteriosus	DIS9P8YS	Strong	Genetic Variation	[23]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[14]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[14]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[14]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[24]
Wilms tumor	DISB6T16	Strong	Altered Expression	[25]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[26]
Obsolete megacystis-microcolon-intestinal hypoperistalsis syndrome	DISP6WWH	Supportive	Autosomal dominant	[18]
Trichohepatoenteric syndrome	DISL3ODF	Disputed	Genetic Variation	[27]
Acute leukaemia	DISDQFDI	Limited	Genetic Variation	[28]
Asthma	DISW9QNS	Limited	Altered Expression	[29]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Biomarker	[30]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[16]
Megacystis-microcolon-intestinal hypoperistalsis syndrome	DIS9KV47	Limited	Biomarker	[32]
Peutz-Jeghers syndrome	DISF27ZJ	Limited	Genetic Variation	[15]
Visceral myopathy 2	DISQPZCZ	Limited	Autosomal dominant	[33]

15 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-11 (MYH11).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myosin-11 (MYH11).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myosin-11 (MYH11).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myosin-11 (MYH11).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Myosin-11 (MYH11).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Myosin-11 (MYH11).	[40]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myosin-11 (MYH11).	[41]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Myosin-11 (MYH11).	[38]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Myosin-11 (MYH11).	[42]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Myosin-11 (MYH11).	[43]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the expression of Myosin-11 (MYH11).	[44]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Myosin-11 (MYH11).	[45]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Myosin-11 (MYH11).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Myosin-11 (MYH11).	[49]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Myosin-11 (MYH11).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Myosin-11 (MYH11).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Myosin-11 (MYH11).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Myosin-11 (MYH11).	[47]

References

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