Molecule Information

General Information of the Molecule (ID: Mol04138)

• Name: Neurofibromin 1 (NF1) ,Homo sapiens
• Synonyms: Neurofibromatosis-related protein NF-1
• Molecule Type: Protein
• Gene Name: NF1
• Gene ID: 4763
• Location: chr17:31094927-31382116[+]
• 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
• 3D-structure: PDB ID: 7PGP; Classification: Signaling protein; Method: Electron microscopy; Resolution: 3.10 Å
• 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. .
• Uniprot ID: NF1_HUMAN
• Ensembl ID: ENSG00000196712
• HGNC ID: HGNC:7765

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Everolimus

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: Everolimus
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

Tamoxifen

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: Tamoxifen
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

Clinical Trial Drug(s) 2 drug(s) in total

Cobimetinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: Cobimetinib
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

2DG

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: 2DG
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

Discontinued Drug(s) 2 drug(s) in total

Etomoxir

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: Etomoxir
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

PF-04620110

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: PF-04620110
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

Preclinical Drug(s) 2 drug(s) in total

BPTES

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: BPTES
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

PF-06424439

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: ER+ breast adenocarcinoma [ICD-11: 2C61.1] [1]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: ER+ breast adenocarcinoma [ICD-11: 2C61.1]
• Sensitive Drug: PF-06424439
• Molecule Alteration: Mutation; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Rat, with ER + MCF7 cell lines; Rats
• Experiment for Molecule Alteration: LC-MS
• Experiment for Drug Resistance: Incucyte proliferation assay
• Mechanism Description: Lastly,NF1deficiency alters the synergy between metabolic inhibitors and traditional targeted inhibitors. This includes increased synergy with inhibitors targeting glycolysis, glutamine metabolism, mitochondrial fatty acid transport, and TG synthesis.

References

• Ref 1: NF1 deficiency drives metabolic reprogramming in ER+ breast cancer. Mol Metab. 2024 Feb;80:101876.