Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS4MJZ7)

• DOT Name: Protein kinase C-binding protein NELL2 (NELL2)
• Synonyms: NEL-like protein 2; Nel-related protein 2
• Gene Name: NELL2
• Related Disease:
  Benign prostatic hyperplasia
  Ependymoma
  Acute myelogenous leukaemia
  Adult glioblastoma
  Advanced cancer
  Chronic eosinophilic leukemia
  Chronic myelomonocytic leukaemia
  Chronic myelomonocytic leukemia
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Glioblastoma multiforme
  Lung adenocarcinoma
  Mast cell leukaemia
  Myeloid leukaemia
  Neoplasm
  Neuroblastoma
  Neuroepithelial neoplasm
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Systemic mastocytosis
  Epithelial ovarian cancer
  Atopic dermatitis
  Intellectual disability
  Leukoplakia
• UniProt ID: NELL2_HUMAN
• PDB ID: 6POG
• Pfam ID: PF12947 ; PF07645 ; PF02210 ; PF00093
• Sequence:
  MESRVLLRTFCLIFGLGAVWGLGVDPSLQIDVLTELELGESTTGVRQVPGLHNGTKAFLF
  QDTPRSIKASTATAEQFFQKLRNKHEFTILVTLKQTHLNSGVILSIHHLDHRYLELESSG
  HRNEVRLHYRSGSHRPHTEVFPYILADDKWHKLSLAISASHLILHIDCNKIYERVVEKPS
  TDLPLGTTFWLGQRNNAHGYFKGIMQDVQLLVMPQGFIAQCPDLNRTCPTCNDFHGLVQK
  IMELQDILAKTSAKLSRAEQRMNRLDQCYCERTCTMKGTTYREFESWIDGCKNCTCLNGT
  IQCETLICPNPDCPLKSALAYVDGKCCKECKSICQFQGRTYFEGERNTVYSSSGVCVLYE
  CKDQTMKLVESSGCPALDCPESHQITLSHSCCKVCKGYDFCSERHNCMENSICRNLNDRA
  VCSCRDGFRALREDNAYCEDIDECAEGRHYCRENTMCVNTPGSFMCICKTGYIRIDDYSC
  TEHDECITNQHNCDENALCFNTVGGHNCVCKPGYTGNGTTCKAFCKDGCRNGGACIAANV
  CACPQGFTGPSCETDIDECSDGFVQCDSRANCINLPGWYHCECRDGYHDNGMFSPSGESC
  EDIDECGTGRHSCANDTICFNLDGGYDCRCPHGKNCTGDCIHDGKVKHNGQIWVLENDRC
  SVCSCQNGFVMCRRMVCDCENPTVDLFCCPECDPRLSSQCLHQNGETLYNSGDTWVQNCQ
  QCRCLQGEVDCWPLPCPDVECEFSILPENECCPRCVTDPCQADTIRNDITKTCLDEMNVV
  RFTGSSWIKHGTECTLCQCKNGHICCSVDPQCLQEL
• Function: Plays multiple roles in neural tissues, regulates neuronal proliferation, survival, differentiation, polarization, as well as axon guidance and synaptic functions. Plays an important role in axon development during neuronal differentiation through the MAPK intracellular signaling pathway. Via binding to its receptor ROBO3, plays a role in axon guidance, functioning as a repulsive axon guidance cue that contributes to commissural axon guidance to the midline. Required for neuron survival through the modulation of MAPK signaling pathways too. Involved in the regulation of hypothalamic GNRH secretion and the control of puberty; Epididymal-secreted protein that signals through a ROS1-pathway to regulate the epididymal initial segment (IS) maturation, sperm maturation and male fertility.
• Reactome Pathway: Regulation of commissural axon pathfinding by SLIT and ROBO (R-HSA-428542)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Definitive	Altered Expression	[1]
Ependymoma	DISUMRNZ	Definitive	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Chronic eosinophilic leukemia	DISAJOUO	Strong	Biomarker	[3]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Biomarker	[3]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[5]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[5]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[4]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[8]
Mast cell leukaemia	DIS7VQW9	Strong	Biomarker	[3]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[4]
Neuroepithelial neoplasm	DISCYKLP	Strong	Altered Expression	[4]
Prostate cancer	DISF190Y	Strong	Altered Expression	[10]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[10]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[6]
Systemic mastocytosis	DISNQ2OY	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[11]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[12]
Intellectual disability	DISMBNXP	Limited	Biomarker	[13]
Leukoplakia	DIST3QD3	Limited	Genetic Variation	[14]

18 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 Protein kinase C-binding protein NELL2 (NELL2).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein kinase C-binding protein NELL2 (NELL2).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[21]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[22]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[23]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein kinase C-binding protein NELL2 (NELL2).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[22]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[22]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[25]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein kinase C-binding protein NELL2 (NELL2).	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein kinase C-binding protein NELL2 (NELL2).	[26]

References

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• [19] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [20] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
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• [23] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [24] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
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• [26] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
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