Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRFC3IJ)

• DOT Name: Myoferlin (MYOF)
• Synonyms: Fer-1-like protein 3
• Gene Name: MYOF
• Related Disease:
  Cardiomyopathy
  Matthew-Wood syndrome
  Acute myelogenous leukaemia
  Autosomal recessive limb-girdle muscular dystrophy type 2B
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Head and neck cancer
  Head and neck carcinoma
  Oropharyngeal squamous cell carcinoma
  Osteoarthritis
  Hepatocellular carcinoma
  Limb-girdle muscular dystrophy
  Metastatic malignant neoplasm
  Muscular dystrophy
  Angioedema, hereditary, 7
  Clear cell renal carcinoma
  Melanoma
  Neoplasm
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Triple negative breast cancer
• UniProt ID: MYOF_HUMAN
• PDB ID: 2DMH; 2K2O; 6EEL
• Pfam ID: PF00168 ; PF08165 ; PF08150 ; PF08151 ; PF16165
• Sequence:
  MLRVIVESASNIPKTKFGKPDPIVSVIFKDEKKKTKKVDNELNPVWNEILEFDLRGIPLD
  FSSSLGIIVKDFETIGQNKLIGTATVALKDLTGDQSRSLPYKLISLLNEKGQDTGATIDL
  VIGYDPPSAPHPNDLSGPSVPGMGGDGEEDEGDEDRLDNAVRGPGPKGPVGTVSEAQLAR
  RLTKVKNSRRMLSNKPQDFQIRVRVIEGRQLSGNNIRPVVKVHVCGQTHRTRIKRGNNPF
  FDELFFYNVNMTPSELMDEIISIRVYNSHSLRADCLMGEFKIDVGFVYDEPGHAVMRKWL
  LLNDPEDTSSGSKGYMKVSMFVLGTGDEPPPERRDRDNDSDDVESNLLLPAGIALRWVTF
  LLKIYRAEDIPQMDDAFSQTVKEIFGGNADKKNLVDPFVEVSFAGKKVCTNIIEKNANPE
  WNQVVNLQIKFPSVCEKIKLTIYDWDRLTKNDVVGTTYLHLSKIAASGGEVEDFSSSGTG
  AASYTVNTGETEVGFVPTFGPCYLNLYGSPREYTGFPDPYDELNTGKGEGVAYRGRILVE
  LATFLEKTPPDKKLEPISNDDLLVVEKYQRRRKYSLSAVFHSATMLQDVGEAIQFEVSIG
  NYGNKFDTTCKPLASTTQYSRAVFDGNYYYYLPWAHTKPVVTLTSYWEDISHRLDAVNTL
  LAMAERLQTNIEALKSGIQGKIPANQLAELWLKLIDEVIEDTRYTLPLTEGKANVTVLDT
  QIRKLRSRSLSQIHEAAVRMRSEATDVKSTLAEIEDWLDKLMQLTEEPQNSMPDIIIWMI
  RGEKRLAYARIPAHQVLYSTSGENASGKYCGKTQTIFLKYPQEKNNGPKVPVELRVNIWL
  GLSAVEKKFNSFAEGTFTVFAEMYENQALMFGKWGTSGLVGRHKFSDVTGKIKLKREFFL
  PPKGWEWEGEWIVDPERSLLTEADAGHTEFTDEVYQNESRYPGGDWKPAEDTYTDANGDK
  AASPSELTCPPGWEWEDDAWSYDINRAVDEKGWEYGITIPPDHKPKSWVAAEKMYHTHRR
  RRLVRKRKKDLTQTASSTARAMEELQDQEGWEYASLIGWKFHWKQRSSDTFRRRRWRRKM
  APSETHGAAAIFKLEGALGADTTEDGDEKSLEKQKHSATTVFGANTPIVSCNFDRVYIYH
  LRCYVYQARNLLALDKDSFSDPYAHICFLHRSKTTEIIHSTLNPTWDQTIIFDEVEIYGE
  PQTVLQNPPKVIMELFDNDQVGKDEFLGRSIFSPVVKLNSEMDITPKLLWHPVMNGDKAC
  GDVLVTAELILRGKDGSNLPILPPQRAPNLYMVPQGIRPVVQLTAIEILAWGLRNMKNFQ
  MASITSPSLVVECGGERVESVVIKNLKKTPNFPSSVLFMKVFLPKEELYMPPLVIKVIDH
  RQFGRKPVVGQCTIERLDRFRCDPYAGKEDIVPQLKASLLSAPPCRDIVIEMEDTKPLLA
  SKLTEKEEEIVDWWSKFYASSGEHEKCGQYIQKGYSKLKIYNCELENVAEFEGLTDFSDT
  FKLYRGKSDENEDPSVVGEFKGSFRIYPLPDDPSVPAPPRQFRELPDSVPQECTVRIYIV
  RGLELQPQDNNGLCDPYIKITLGKKVIEDRDHYIPNTLNPVFGRMYELSCYLPQEKDLKI
  SVYDYDTFTRDEKVGETIIDLENRFLSRFGSHCGIPEEYCVSGVNTWRDQLRPTQLLQNV
  ARFKGFPQPILSEDGSRIRYGGRDYSLDEFEANKILHQHLGAPEERLALHILRTQGLVPE
  HVETRTLHSTFQPNISQGKLQMWVDVFPKSLGPPGPPFNITPRKAKKYYLRVIIWNTKDV
  ILDEKSITGEEMSDIYVKGWIPGNEENKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEQL
  CIVAKKEHFWSIDQTEFRIPPRLIIQIWDNDKFSLDDYLGFLELDLRHTIIPAKSPEKCR
  LDMIPDLKAMNPLKAKTASLFEQKSMKGWWPCYAEKDGARVMAGKVEMTLEILNEKEADE
  RPAGKGRDEPNMNPKLDLPNRPETSFLWFTNPCKTMKFIVWRRFKWVIIGLLFLLILLLF
  VAVLLYSLPNYLSMKIVKPNV
• Function: Calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress. Involved in endocytic recycling. Implicated in VEGF signal transduction by regulating the levels of the receptor KDR.
• Tissue Specificity: Expressed in myoblast and endothelial cells (at protein level). Highly expressed in cardiac and skeletal muscles. Also present in lung, and at very low levels in kidney, placenta and brain.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiomyopathy	DISUPZRG	Definitive	Genetic Variation	[1]
Matthew-Wood syndrome	DISA7HR7	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Autosomal recessive limb-girdle muscular dystrophy type 2B	DISWWCL7	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Head and neck cancer	DISBPSQZ	Strong	Altered Expression	[8]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[8]
Oropharyngeal squamous cell carcinoma	DIS7D7QV	Strong	Altered Expression	[8]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[9]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[10]
Limb-girdle muscular dystrophy	DISI9Y1Z	moderate	Genetic Variation	[1]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[11]
Muscular dystrophy	DISJD6P7	moderate	Biomarker	[12]
Angioedema, hereditary, 7	DISAIGH7	Limited	Unknown	[13]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[14]
Melanoma	DIS1RRCY	Limited	Altered Expression	[15]
Neoplasm	DISZKGEW	Limited	Altered Expression	[7]
Pancreatic cancer	DISJC981	Limited	Biomarker	[16]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[17]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Myoferlin (MYOF).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myoferlin (MYOF).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myoferlin (MYOF).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myoferlin (MYOF).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Myoferlin (MYOF).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Myoferlin (MYOF).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myoferlin (MYOF).	[24]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Myoferlin (MYOF).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Myoferlin (MYOF).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Myoferlin (MYOF).	[27]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Myoferlin (MYOF).	[28]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Myoferlin (MYOF).	[29]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Myoferlin (MYOF).	[30]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Myoferlin (MYOF).	[31]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Myoferlin (MYOF).	[28]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Myoferlin (MYOF).	[32]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of Myoferlin (MYOF).	[33]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Myoferlin (MYOF).	[34]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Myoferlin (MYOF).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Myoferlin (MYOF).	[28]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Myoferlin (MYOF).	[36]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Myoferlin (MYOF).	[37]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Myoferlin (MYOF).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Myoferlin (MYOF).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myoferlin (MYOF).	[40]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Myoferlin (MYOF).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myoferlin (MYOF).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Myoferlin (MYOF).	[42]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Myoferlin (MYOF).	[43]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Myoferlin (MYOF).	[44]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Myoferlin (MYOF).	[45]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Myoferlin (MYOF).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the binding of Myoferlin (MYOF).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Myoferlin (MYOF).	[39]

References

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• [16] Modification and Biological Evaluation of a Series of 1,5-Diaryl-1,2,4-triazole Compounds as Novel Agents against Pancreatic Cancer Metastasis through Targeting Myoferlin.J Med Chem. 2019 May 23;62(10):4949-4966. doi: 10.1021/acs.jmedchem.9b00059. Epub 2019 May 8.
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