Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC29NHH)

• DOT Name: Neurofibromin (NF1)
• Synonyms: Neurofibromatosis-related protein NF-1
• Gene Name: NF1
• Related Disease:
  Mixed glioma
  Neurofibromatosis type 1
  Neurofibromatosis, familial spinal
  Neurofibromatosis-Noonan syndrome
  Watson syndrome
  Acute myelogenous leukaemia
  Breast cancer
  Colorectal carcinoma
  Cutaneous melanoma
  Dedifferentiated liposarcoma
  Fibrosarcoma
  Glioma
  Liposarcoma
  Malignant peripheral nerve sheath tumor
  Melanoma
  Nerve sheath neoplasm
  Noonan syndrome
  Pheochromocytoma
  Pleomorphic sarcoma
  Anaplastic astrocytoma
  Moyamoya disease
  Oligoastrocytoma
  Sarcoma
  Schwannoma
  Hereditary pheochromocytoma-paraganglioma
  Adenoma
  Autism
  Malignant glioma
  Melanocytic nevus
  Astrocytoma
  Intellectual disability
  Leukemia
  Familial ovarian cancer
• UniProt ID: NF1_HUMAN
• PDB ID: 1NF1; 2D4Q; 2E2X; 3P7Z; 3PEG; 3PG7; 6OB2; 6OB3; 6V65; 6V6F; 7MOC; 7MP5; 7MP6; 7PGP; 7PGQ; 7PGR; 7PGS; 7PGT; 7PGU; 7R03; 7R04; 8E20; 8EDL; 8EDM; 8EDN; 8EDO
• Pfam ID: PF13716 ; PF00616
• Sequence:
  MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLINISKYKFSLVISGLTT
  ILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKCLAGQPKDTMRLDETMLVKQLLPEICHF
  LHTCREGNQHAAELRNSASGVLFSLSCNNFNAVFSRISTRLQELTVCSEDNVDVHDIELL
  QYINVDCAKLKRLLKETAFKFKALKKVAQLAVINSLEKAFWNWVENYPDEFTKLYQIPQT
  DMAECAEKLFDLVDGFAESTKRKAAVWPLQIILLILCPEIIQDISKDVVDENNMNKKLFL
  DSLRKALAGHGGSRQLTESAAIACVKLCKASTYINWEDNSVIFLLVQSMVVDLKNLLFNP
  SKPFSRGSQPADVDLMIDCLVSCFRISPHNNQHFKICLAQNSPSTFHYVLVNSLHRIITN
  SALDWWPKIDAVYCHSVELRNMFGETLHKAVQGCGAHPAIRMAPSLTFKEKVTSLKFKEK
  PTDLETRSYKYLLLSMVKLIHADPKLLLCNPRKQGPETQGSTAELITGLVQLVPQSHMPE
  IAQEAMEALLVLHQLDSIDLWNPDAPVETFWEISSQMLFYICKKLTSHQMLSSTEILKWL
  REILICRNKFLLKNKQADRSSCHFLLFYGVGCDIPSSGNTSQMSMDHEELLRTPGASLRK
  GKGNSSMDSAAGCSGTPPICRQAQTKLEVALYMFLWNPDTEAVLVAMSCFRHLCEEADIR
  CGVDEVSVHNLLPNYNTFMEFASVSNMMSTGRAALQKRVMALLRRIEHPTAGNTEAWEDT
  HAKWEQATKLILNYPKAKMEDGQAAESLHKTIVKRRMSHVSGGGSIDLSDTDSLQEWINM
  TGFLCALGGVCLQQRSNSGLATYSPPMGPVSERKGSMISVMSSEGNADTPVSKFMDRLLS
  LMVCNHEKVGLQIRTNVKDLVGLELSPALYPMLFNKLKNTISKFFDSQGQVLLTDTNTQF
  VEQTIAIMKNLLDNHTEGSSEHLGQASIETMMLNLVRYVRVLGNMVHAIQIKTKLCQLVE
  VMMARRDDLSFCQEMKFRNKMVEYLTDWVMGTSNQAADDDVKCLTRDLDQASMEAVVSLL
  AGLPLQPEEGDGVELMEAKSQLFLKYFTLFMNLLNDCSEVEDESAQTGGRKRGMSRRLAS
  LRHCTVLAMSNLLNANVDSGLMHSIGLGYHKDLQTRATFMEVLTKILQQGTEFDTLAETV
  LADRFERLVELVTMMGDQGELPIAMALANVVPCSQWDELARVLVTLFDSRHLLYQLLWNM
  FSKEVELADSMQTLFRGNSLASKIMTFCFKVYGATYLQKLLDPLLRIVITSSDWQHVSFE
  VDPTRLEPSESLEENQRNLLQMTEKFFHAIISSSSEFPPQLRSVCHCLYQATCHSLLNKA
  TVKEKKENKKSVVSQRFPQNSIGAVGSAMFLRFINPAIVSPYEAGILDKKPPPRIERGLK
  LMSKILQSIANHVLFTKEEHMRPFNDFVKSNFDAARRFFLDIASDCPTSDAVNHSLSFIS
  DGNVLALHRLLWNNQEKIGQYLSSNRDHKAVGRRPFDKMATLLAYLGPPEHKPVADTHWS
  SLNLTSSKFEEFMTRHQVHEKEEFKALKTLSIFYQAGTSKAGNPIFYYVARRFKTGQING
  DLLIYHVLLTLKPYYAKPYEIVVDLTHTGPSNRFKTDFLSKWFVVFPGFAYDNVSAVYIY
  NCNSWVREYTKYHERLLTGLKGSKRLVFIDCPGKLAEHIEHEQQKLPAATLALEEDLKVF
  HNALKLAHKDTKVSIKVGSTAVQVTSAERTKVLGQSVFLNDIYYASEIEEICLVDENQFT
  LTIANQGTPLTFMHQECEAIVQSIIHIRTRWELSQPDSIPQHTKIRPKDVPGTLLNIALL
  NLGSSDPSLRSAAYNLLCALTCTFNLKIEGQLLETSGLCIPANNTLFIVSISKTLAANEP
  HLTLEFLEECISGFSKSSIELKHLCLEYMTPWLSNLVRFCKHNDDAKRQRVTAILDKLIT
  MTINEKQMYPSIQAKIWGSLGQITDLLDVVLDSFIKTSATGGLGSIKAEVMADTAVALAS
  GNVKLVSSKVIGRMCKIIDKTCLSPTPTLEQHLMWDDIAILARYMLMLSFNNSLDVAAHL
  PYLFHVVTFLVATGPLSLRASTHGLVINIIHSLCTCSQLHFSEETKQVLRLSLTEFSLPK
  FYLLFGISKVKSAAVIAFRSSYRDRSFSPGSYERETFALTSLETVTEALLEIMEACMRDI
  PTCKWLDQWTELAQRFAFQYNPSLQPRALVVFGCISKRVSHGQIKQIIRILSKALESCLK
  GPDTYNSQVLIEATVIALTKLQPLLNKDSPLHKALFWVAVAVLQLDEVNLYSAGTALLEQ
  NLHTLDSLRIFNDKSPEEVFMAIRNPLEWHCKQMDHFVGLNFNSNFNFALVGHLLKGYRH
  PSPAIVARTVRILHTLLTLVNKHRNCDKFEVNTQSVAYLAALLTVSEEVRSRCSLKHRKS
  LLLTDISMENVPMDTYPIHHGDPSYRTLKETQPWSSPKGSEGYLAATYPTVGQTSPRARK
  SMSLDMGQPSQANTKKLLGTRKSFDHLISDTKAPKRQEMESGITTPPKMRRVAETDYEME
  TQRISSSQQHPHLRKVSVSESNVLLDEEVLTDPKIQALLLTVLATLVKYTTDEFDQRILY
  EYLAEASVVFPKVFPVVHNLLDSKINTLLSLCQDPNLLNPIHGIVQSVVYHEESPPQYQT
  SYLQSFGFNGLWRFAGPFSKQTQIPDYAELIVKFLDALIDTYLPGIDEETSEESLLTPTS
  PYPPALQSQLSITANLNLSNSMTSLATSQHSPGIDKENVELSPTTGHCNSGRTRHGSASQ
  VQKQRSAGSFKRNSIKKIV
• Function: Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity.
• Tissue Specificity: Detected in brain, peripheral nerve, lung, colon and muscle.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
• Reactome Pathway:
  RAS signaling downstream of NF1 loss-of-function variants (R-HSA-6802953)
  Regulation of RAS by GAPs (R-HSA-5658442)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mixed glioma	DIS64UY3	Definitive	Biomarker	[1]
Neurofibromatosis type 1	DIS53JH9	Definitive	Autosomal dominant	[2]
Neurofibromatosis, familial spinal	DISUNPXT	Definitive	Autosomal dominant	[3]
Neurofibromatosis-Noonan syndrome	DISNOZ2M	Definitive	Autosomal dominant	[4]
Watson syndrome	DIS8ZGU7	Definitive	Autosomal dominant	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[6]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[8]
Cutaneous melanoma	DIS3MMH9	Strong	Biomarker	[9]
Dedifferentiated liposarcoma	DISYJUCJ	Strong	Biomarker	[10]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Genetic Variation	[11]
Liposarcoma	DIS8IZVM	Strong	Genetic Variation	[12]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[13]
Melanoma	DIS1RRCY	Strong	Biomarker	[14]
Nerve sheath neoplasm	DISJYLBY	Strong	Biomarker	[15]
Noonan syndrome	DIS7Q7DN	Strong	Genetic Variation	[16]
Pheochromocytoma	DIS56IFV	Strong	Biomarker	[17]
Pleomorphic sarcoma	DISXU8CC	Strong	Biomarker	[18]
Anaplastic astrocytoma	DISSBE0K	moderate	Biomarker	[19]
Moyamoya disease	DISO62CA	Moderate	Autosomal dominant	[20]
Oligoastrocytoma	DISQGE8F	moderate	Biomarker	[19]
Sarcoma	DISZDG3U	moderate	Biomarker	[18]
Schwannoma	DISTTVLA	moderate	Biomarker	[1]
Hereditary pheochromocytoma-paraganglioma	DISP9K7L	Supportive	Autosomal dominant	[21]
Adenoma	DIS78ZEV	Disputed	Biomarker	[1]
Autism	DISV4V1Z	Disputed	Genetic Variation	[22]
Malignant glioma	DISFXKOV	Disputed	Biomarker	[1]
Melanocytic nevus	DISYS32D	Disputed	Biomarker	[1]
Astrocytoma	DISL3V18	Limited	Biomarker	[23]
Intellectual disability	DISMBNXP	Limited	Biomarker	[24]
Leukemia	DISNAKFL	Limited	Altered Expression	[25]
Familial ovarian cancer	DISGLR2C	No Known	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Neurofibromin (NF1) affects the response to substance of Afimoxifene.	[47]

6 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 Neurofibromin (NF1).	[26]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Neurofibromin (NF1).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Neurofibromin (NF1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Neurofibromin (NF1).	[40]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Neurofibromin (NF1).	[32]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Neurofibromin (NF1).	[43]

22 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 Neurofibromin (NF1).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neurofibromin (NF1).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neurofibromin (NF1).	[29]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Neurofibromin (NF1).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neurofibromin (NF1).	[31]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Neurofibromin (NF1).	[33]
Marinol	DM70IK5	Approved	Marinol increases the expression of Neurofibromin (NF1).	[34]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Neurofibromin (NF1).	[35]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Neurofibromin (NF1).	[36]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Neurofibromin (NF1).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Neurofibromin (NF1).	[35]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Neurofibromin (NF1).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Neurofibromin (NF1).	[38]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Neurofibromin (NF1).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neurofibromin (NF1).	[41]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Neurofibromin (NF1).	[38]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Neurofibromin (NF1).	[42]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Neurofibromin (NF1).	[38]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Neurofibromin (NF1).	[44]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Neurofibromin (NF1).	[45]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Neurofibromin (NF1).	[38]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal decreases the expression of Neurofibromin (NF1).	[46]

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