Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI4X44G)

• DOT Name: Achaete-scute homolog 1 (ASCL1)
• Synonyms: ASH-1; hASH1; Class A basic helix-loop-helix protein 46; bHLHa46
• Gene Name: ASCL1
• Related Disease:
  Lung neoplasm
  Adenoma
  Astrocytoma
  Brain neoplasm
  Breast cancer
  Carcinoid tumor
  Carcinoma
  Cervical Intraepithelial neoplasia
  Digestive system neuroendocrine tumor, grade 1/2
  Epilepsy
  Glioma
  Hyperplasia
  Intellectual disability
  Lung adenocarcinoma
  Medullary thyroid gland carcinoma
  Medulloblastoma
  Neoplasm
  Neuroblastoma
  Obesity
  Parkinson disease
  Pheochromocytoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Schizophrenia
  Stroke
  Thyroid tumor
  Adenocarcinoma
  Haddad syndrome
  Lung carcinoma
  Adult glioblastoma
  Advanced cancer
  Breast carcinoma
  Central hypoventilation syndrome, congenital
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hirschsprung disease
  Lymphoma
  Nervous system disease
  Neuroendocrine neoplasm
  Non-small-cell lung cancer
  Small-cell lung cancer
  Squamous cell carcinoma
  Status epilepticus seizure
• UniProt ID: ASCL1_HUMAN
• Pfam ID: PF00010
• Sequence:
  MESSAKMESGGAGQQPQPQPQQPFLPPAACFFATAAAAAAAAAAAAAQSAQQQQQQQQQQ
  QQAPQLRPAADGQPSGGGHKSAPKQVKRQRSSSPELMRCKRRLNFSGFGYSLPQQQPAAV
  ARRNERERNRVKLVNLGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLDEHDAV
  SAAFQAGVLSPTISPNYSNDLNSMAGSPVSSYSSDEGSYDPLSPEEQELLDFTNWF
• Function: Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways. Directly binds the E box motif (5'-CANNTG-3') on promoters and promotes transcription of neuronal genes. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Plays a role at early stages of development of specific neural lineages in most regions of the CNS, and of several lineages in the PNS. Essential for the generation of olfactory and autonomic neurons. Acts synergistically with FOXN4 to specify the identity of V2b neurons rather than V2a from bipotential p2 progenitors during spinal cord neurogenesis, probably through DLL4-NOTCH signaling activation. Involved in the regulation of neuroendocrine cell development in the glandular stomach.
• Reactome Pathway: NGF-stimulated transcription (R-HSA-9031628)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung neoplasm	DISVARNB	Definitive	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Carcinoid tumor	DISMNRDC	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[5]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[7]
Digestive system neuroendocrine tumor, grade 1/2	DISDR98B	Strong	Biomarker	[8]
Epilepsy	DISBB28L	Strong	Biomarker	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Hyperplasia	DISK4DFB	Strong	Biomarker	[11]
Intellectual disability	DISMBNXP	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Altered Expression	[14]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Biomarker	[17]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[18]
Pheochromocytoma	DIS56IFV	Strong	Altered Expression	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[21]
Schizophrenia	DISSRV2N	Strong	Biomarker	[22]
Stroke	DISX6UHX	Strong	Altered Expression	[23]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[24]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[25]
Haddad syndrome	DISF128S	Supportive	Autosomal dominant	[26]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[27]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[28]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[28]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[6]
Central hypoventilation syndrome, congenital	DISQRK53	Limited	Genetic Variation	[29]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[28]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[30]
Hirschsprung disease	DISUUSM1	Limited	Genetic Variation	[31]
Lymphoma	DISN6V4S	Limited	Altered Expression	[32]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[33]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[34]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[35]
Small-cell lung cancer	DISK3LZD	Limited	Biomarker	[36]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[6]
Status epilepticus seizure	DISY3BIC	Limited	Biomarker	[37]

13 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 Achaete-scute homolog 1 (ASCL1).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Achaete-scute homolog 1 (ASCL1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Achaete-scute homolog 1 (ASCL1).	[40]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Achaete-scute homolog 1 (ASCL1).	[41]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of Achaete-scute homolog 1 (ASCL1).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Achaete-scute homolog 1 (ASCL1).	[43]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Achaete-scute homolog 1 (ASCL1).	[44]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Achaete-scute homolog 1 (ASCL1).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Achaete-scute homolog 1 (ASCL1).	[47]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Achaete-scute homolog 1 (ASCL1).	[48]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Achaete-scute homolog 1 (ASCL1).	[49]
Propanoic Acid	DM9TN2W	Investigative	Propanoic Acid decreases the expression of Achaete-scute homolog 1 (ASCL1).	[50]
eucalyptol	DME5CK3	Investigative	eucalyptol decreases the expression of Achaete-scute homolog 1 (ASCL1).	[51]

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 Achaete-scute homolog 1 (ASCL1).	[45]

References

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• [51] Transcriptome Analysis Reveals the Anti-Tumor Mechanism of Eucalyptol Treatment on Neuroblastoma Cell Line SH-SY5Y. Neurochem Res. 2022 Dec;47(12):3854-3862. doi: 10.1007/s11064-022-03786-8. Epub 2022 Nov 4.