Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT94Z706)

• DOT Name: Myosin-9 (MYH9)
• Synonyms: Cellular myosin heavy chain, type A; Myosin heavy chain 9; Myosin heavy chain, non-muscle IIa; Non-muscle myosin heavy chain A; NMMHC-A; Non-muscle myosin heavy chain IIa; NMMHC II-a; NMMHC-IIA
• Gene Name: MYH9
• Related Disease:
  Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss
  Sickle-cell anaemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Alport syndrome
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autosomal dominant macrothrombocytopenia
  Autosomal dominant nonsyndromic hearing loss 17
  Bernard-Soulier syndrome
  Breast cancer
  Breast lobular carcinoma
  Breast neoplasm
  Cataract
  Clear cell renal carcinoma
  Colorectal carcinoma
  Deafness
  Epithelial ovarian cancer
  Glomerulonephritis
  Hereditary nephritis
  Kidney failure
  Lung cancer
  Lung carcinoma
  Meier-Gorlin syndrome
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Nephritis
  Non-small-cell lung cancer
  Obsolete May-Hegglin anomaly
  Renal cell carcinoma
  Thrombocytopenia
  Thrombocytopenia 2
  Type-1/2 diabetes
  Gastric cancer
  Inherited bleeding disorder, platelet-type
  Metabolic acidosis
  Pancreatic cancer
  Stomach cancer
  Autosomal dominant nonsyndromic hearing loss
  High blood pressure
  Advanced cancer
  Breast carcinoma
  Diabetic kidney disease
  Lupus nephritis
  Non-insulin dependent diabetes
• UniProt ID: MYH9_HUMAN
• PDB ID: 2LNK; 3ZWH; 4CFQ; 4CFR; 4ETO
• Pfam ID: PF00063 ; PF02736 ; PF01576
• Sequence:
  MAQQAADKYLYVDKNFINNPLAQADWAAKKLVWVPSDKSGFEPASLKEEVGEEAIVELVE
  NGKKVKVNKDDIQKMNPPKFSKVEDMAELTCLNEASVLHNLKERYYSGLIYTYSGLFCVV
  INPYKNLPIYSEEIVEMYKGKKRHEMPPHIYAITDTAYRSMMQDREDQSILCTGESGAGK
  TENTKKVIQYLAYVASSHKSKKDQGELERQLLQANPILEAFGNAKTVKNDNSSRFGKFIR
  INFDVNGYIVGANIETYLLEKSRAIRQAKEERTFHIFYYLLSGAGEHLKTDLLLEPYNKY
  RFLSNGHVTIPGQQDKDMFQETMEAMRIMGIPEEEQMGLLRVISGVLQLGNIVFKKERNT
  DQASMPDNTAAQKVSHLLGINVTDFTRGILTPRIKVGRDYVQKAQTKEQADFAIEALAKA
  TYERMFRWLVLRINKALDKTKRQGASFIGILDIAGFEIFDLNSFEQLCINYTNEKLQQLF
  NHTMFILEQEEYQREGIEWNFIDFGLDLQPCIDLIEKPAGPPGILALLDEECWFPKATDK
  SFVEKVMQEQGTHPKFQKPKQLKDKADFCIIHYAGKVDYKADEWLMKNMDPLNDNIATLL
  HQSSDKFVSELWKDVDRIIGLDQVAGMSETALPGAFKTRKGMFRTVGQLYKEQLAKLMAT
  LRNTNPNFVRCIIPNHEKKAGKLDPHLVLDQLRCNGVLEGIRICRQGFPNRVVFQEFRQR
  YEILTPNSIPKGFMDGKQACVLMIKALELDSNLYRIGQSKVFFRAGVLAHLEEERDLKIT
  DVIIGFQACCRGYLARKAFAKRQQQLTAMKVLQRNCAAYLKLRNWQWWRLFTKVKPLLQV
  SRQEEEMMAKEEELVKVREKQLAAENRLTEMETLQSQLMAEKLQLQEQLQAETELCAEAE
  ELRARLTAKKQELEEICHDLEARVEEEEERCQHLQAEKKKMQQNIQELEEQLEEEESARQ
  KLQLEKVTTEAKLKKLEEEQIILEDQNCKLAKEKKLLEDRIAEFTTNLTEEEEKSKSLAK
  LKNKHEAMITDLEERLRREEKQRQELEKTRRKLEGDSTDLSDQIAELQAQIAELKMQLAK
  KEEELQAALARVEEEAAQKNMALKKIRELESQISELQEDLESERASRNKAEKQKRDLGEE
  LEALKTELEDTLDSTAAQQELRSKREQEVNILKKTLEEEAKTHEAQIQEMRQKHSQAVEE
  LAEQLEQTKRVKANLEKAKQTLENERGELANEVKVLLQGKGDSEHKRKKVEAQLQELQVK
  FNEGERVRTELADKVTKLQVELDNVTGLLSQSDSKSSKLTKDFSALESQLQDTQELLQEE
  NRQKLSLSTKLKQVEDEKNSFREQLEEEEEAKHNLEKQIATLHAQVADMKKKMEDSVGCL
  ETAEEVKRKLQKDLEGLSQRHEEKVAAYDKLEKTKTRLQQELDDLLVDLDHQRQSACNLE
  KKQKKFDQLLAEEKTISAKYAEERDRAEAEAREKETKALSLARALEEAMEQKAELERLNK
  QFRTEMEDLMSSKDDVGKSVHELEKSKRALEQQVEEMKTQLEELEDELQATEDAKLRLEV
  NLQAMKAQFERDLQGRDEQSEEKKKQLVRQVREMEAELEDERKQRSMAVAARKKLEMDLK
  DLEAHIDSANKNRDEAIKQLRKLQAQMKDCMRELDDTRASREEILAQAKENEKKLKSMEA
  EMIQLQEELAAAERAKRQAQQERDELADEIANSSGKGALALEEKRRLEARIAQLEEELEE
  EQGNTELINDRLKKANLQIDQINTDLNLERSHAQKNENARQQLERQNKELKVKLQEMEGT
  VKSKYKASITALEAKIAQLEEQLDNETKERQAACKQVRRTEKKLKDVLLQVDDERRNAEQ
  YKDQADKASTRLKQLKRQLEEAEEEAQRANASRRKLQRELEDATETADAMNREVSSLKNK
  LRRGDLPFVVPRRMARKGAGDGSDEEVDGKADGAEAKPAE
• Function: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis. Promotes cell motility in conjunction with S100A4. During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10.
• Tissue Specificity: In the kidney, expressed in the glomeruli. Also expressed in leukocytes.
• 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:
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  EPHA-mediated growth cone collapse (R-HSA-3928663)
  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)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  CD163 mediating an anti-inflammatory response (R-HSA-9662834)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss	DIS0R0IY	Definitive	Autosomal dominant	[1]
Sickle-cell anaemia	DIS5YNZB	Definitive	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Alport syndrome	DIS25AB4	Strong	Genetic Variation	[5]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[6]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[7]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[7]
Autosomal dominant macrothrombocytopenia	DISUTMSW	Strong	Genetic Variation	[8]
Autosomal dominant nonsyndromic hearing loss 17	DISYYOQH	Strong	Autosomal dominant	[9]
Bernard-Soulier syndrome	DISLD1FU	Strong	Genetic Variation	[10]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[11]
Breast lobular carcinoma	DISBY98Q	Strong	Biomarker	[12]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[12]
Cataract	DISUD7SL	Strong	Biomarker	[13]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[15]
Deafness	DISKCLH4	Strong	Genetic Variation	[16]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[17]
Glomerulonephritis	DISPZIQ3	Strong	Altered Expression	[18]
Hereditary nephritis	DISECBR1	Strong	Biomarker	[19]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[20]
Lung cancer	DISCM4YA	Strong	Biomarker	[21]
Lung carcinoma	DISTR26C	Strong	Biomarker	[21]
Meier-Gorlin syndrome	DISCFIU3	Strong	Genetic Variation	[22]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[23]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[24]
Nephritis	DISQZQ70	Strong	Genetic Variation	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Obsolete May-Hegglin anomaly	DISM4VFR	Strong	Autosomal dominant	[26]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[14]
Thrombocytopenia	DISU61YW	Strong	Genetic Variation	[27]
Thrombocytopenia 2	DISBLVLV	Strong	Genetic Variation	[28]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[29]
Gastric cancer	DISXGOUK	moderate	Biomarker	[30]
Inherited bleeding disorder, platelet-type	DISIUNXT	moderate	Biomarker	[31]
Metabolic acidosis	DIS7UMEC	moderate	Biomarker	[32]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[33]
Stomach cancer	DISKIJSX	moderate	Biomarker	[30]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[34]
High blood pressure	DISY2OHH	Disputed	Genetic Variation	[35]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[36]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[11]
Diabetic kidney disease	DISJMWEY	Limited	Biomarker	[37]
Lupus nephritis	DISCVGPZ	Limited	Genetic Variation	[38]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[39]

5 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-9 (MYH9).	[40]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Myosin-9 (MYH9).	[60]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Myosin-9 (MYH9).	[62]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Myosin-9 (MYH9).	[63]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Myosin-9 (MYH9).	[62]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myosin-9 (MYH9).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myosin-9 (MYH9).	[42]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Myosin-9 (MYH9).	[43]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myosin-9 (MYH9).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myosin-9 (MYH9).	[45]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Myosin-9 (MYH9).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myosin-9 (MYH9).	[46]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Myosin-9 (MYH9).	[47]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Myosin-9 (MYH9).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Myosin-9 (MYH9).	[49]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Myosin-9 (MYH9).	[50]
Selenium	DM25CGV	Approved	Selenium increases the expression of Myosin-9 (MYH9).	[51]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Myosin-9 (MYH9).	[52]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Myosin-9 (MYH9).	[53]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Myosin-9 (MYH9).	[54]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Myosin-9 (MYH9).	[55]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Myosin-9 (MYH9).	[57]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Myosin-9 (MYH9).	[58]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Myosin-9 (MYH9).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Myosin-9 (MYH9).	[61]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myosin-9 (MYH9).	[50]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Myosin-9 (MYH9).	[64]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Myosin-9 (MYH9).	[65]

1 Drug(s) Affected the Biochemical Pathways of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB increases the metabolism of Myosin-9 (MYH9).	[56]

References

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