Details of Drug Off-Target (DOT)

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

• DOT Name: Neurogenin-2 (NEUROG2)
• Synonyms: NGN-2; Class A basic helix-loop-helix protein 8; bHLHa8; Protein atonal homolog 4
• Gene Name: NEUROG2
• Related Disease:
  Adenoma
  Alzheimer disease
  Cerebral infarction
  Medulloblastoma
  Osteoglophonic dwarfism
  Pituitary adenoma
  Schizophrenia
  Stroke
  Nasopharyngeal carcinoma
  Neuroblastoma
  Niemann-Pick disease type C
  Tuberous sclerosis
• UniProt ID: NGN2_HUMAN
• Pfam ID: PF00010
• Sequence:
  MFVKSETLELKEEEDVLVLLGSASPALAALTPLSSSADEEEEEEPGASGGARRQRGAEAG
  QGARGGVAAGAEGCRPARLLGLVHDCKRRPSRARAVSRGAKTAETVQRIKKTRRLKANNR
  ERNRMHNLNAALDALREVLPTFPEDAKLTKIETLRFAHNYIWALTETLRLADHCGGGGGG
  LPGALFSEAVLLSPGGASAALSSSGDSPSPASTWSCTNSPAPSSSVSSNSTSPYSCTLSP
  ASPAGSDMDYWQPPPPDKHRYAPHLPIARDCI
• Function: Transcriptional regulator. Involved in neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3').

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[3]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[4]
Osteoglophonic dwarfism	DISVSNPT	Strong	Altered Expression	[3]
Pituitary adenoma	DISJ5R1X	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[5]
Stroke	DISX6UHX	Strong	Biomarker	[3]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[6]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[6]
Niemann-Pick disease type C	DIS492ZO	moderate	Biomarker	[6]
Tuberous sclerosis	DISEMUGZ	Limited	Altered Expression	[7]

2 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 Neurogenin-2 (NEUROG2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Neurogenin-2 (NEUROG2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neurogenin-2 (NEUROG2).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Neurogenin-2 (NEUROG2).	[10]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Neurogenin-2 (NEUROG2).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Neurogenin-2 (NEUROG2).	[10]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Neurogenin-2 (NEUROG2).	[10]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Neurogenin-2 (NEUROG2).	[10]
Nilotinib	DM7HXWT	Approved	Nilotinib increases the expression of Neurogenin-2 (NEUROG2).	[10]
Abacavir	DMMN36E	Approved	Abacavir increases the expression of Neurogenin-2 (NEUROG2).	[10]
Polyethylene glycol	DM4I1JP	Approved	Polyethylene glycol increases the expression of Neurogenin-2 (NEUROG2).	[10]
Dabigatran	DMDI6R4	Approved	Dabigatran increases the expression of Neurogenin-2 (NEUROG2).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Neurogenin-2 (NEUROG2).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Neurogenin-2 (NEUROG2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Neurogenin-2 (NEUROG2).	[14]

References

• [1] Differential expression of neurogenins and NeuroD1 in human pituitary tumours.J Endocrinol. 2007 Sep;194(3):475-84. doi: 10.1677/JOE-07-0020.
• [2] Differential Roles of Environmental Enrichment in Alzheimer's Type of Neurodegeneration and Physiological Aging.Front Aging Neurosci. 2017 Jul 26;9:245. doi: 10.3389/fnagi.2017.00245. eCollection 2017.
• [3] TAT-Ngn2 Enhances Cognitive Function Recovery and Regulates Caspase-Dependent and Mitochondrial Apoptotic Pathways After Experimental Stroke.Front Cell Neurosci. 2018 Dec 14;12:475. doi: 10.3389/fncel.2018.00475. eCollection 2018.
• [4] Upregulation of SOX2, NOTCH1, and ID1 in supratentorial primitive neuroectodermal tumors: a distinct differentiation pattern from that of medulloblastomas.J Neurosurg Pediatr. 2010 Jun;5(6):608-14. doi: 10.3171/2010.2.PEDS1065.
• [5] Inhibition of STEP(61) ameliorates deficits in mouse and hiPSC-based schizophrenia models.Mol Psychiatry. 2018 Feb;23(2):271-281. doi: 10.1038/mp.2016.163. Epub 2016 Oct 18.
• [6] Neurogenin-2-transduced human neural progenitor cells attenuate neonatal hypoxic-ischemic brain injury.Transl Res. 2017 May;183:121-136.e9. doi: 10.1016/j.trsl.2016.12.010. Epub 2016 Dec 29.
• [7] Biallelic Mutations in TSC2 Lead to Abnormalities Associated with Cortical Tubers in Human iPSC-Derived Neurons.J Neurosci. 2019 Nov 20;39(47):9294-9305. doi: 10.1523/JNEUROSCI.0642-19.2019. Epub 2019 Oct 7.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [10] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [11] Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.