Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT37NXR0)

• DOT Name: TOM1-like protein 1 (TOM1L1)
• Synonyms: Src-activating and signaling molecule protein; Target of Myb-like protein 1
• Gene Name: TOM1L1
• Related Disease:
  Esophageal squamous cell carcinoma
  Prostate cancer
  Prostate neoplasm
  Squamous cell carcinoma
• UniProt ID: TM1L1_HUMAN
• PDB ID: 3RRU
• Pfam ID: PF03127 ; PF00790
• Sequence:
  MAFGKSHRDPYATSVGHLIEKATFAGVQTEDWGQFMHICDIINTTQDGPKDAVKALKKRI
  SKNYNHKEIQLTLSLIDMCVQNCGPSFQSLIVKKEFVKENLVKLLNPRYNLPLDIQNRIL
  NFIKTWSQGFPGGVDVSEVKEVYLDLVKKGVQFPPSEAEAETARQETAQISSNPPTSVPT
  APALSSVIAPKNSTVTLVPEQIGKLHSELDMVKMNVRVMSAILMENTPGSENHEDIELLQ
  KLYKTGREMQERIMDLLVVVENEDVTVELIQVNEDLNNAILGYERFTRNQQRILEQNKNQ
  KEATNTTSEPSAPSQDLLDLSPSPRMPRATLGELNTMNNQLSGLNFSLPSSDVTNNLKPS
  LHPQMNLLALENTEIPPFAQRTSQNLTSSHAYDNFLEHSNSVFLQPVSLQTIAAAPSNQS
  LPPLPSNHPAMTKSDLQPPNYYEVMEFDPLAPAVTTEAIYEEIDAHQHKGAQNDGD
• Function: Probable adapter protein involved in signaling pathways. Interacts with the SH2 and SH3 domains of various signaling proteins when it is phosphorylated. May promote FYN activation, possibly by disrupting intramolecular SH3-dependent interactions.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[3]

10 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 TOM1-like protein 1 (TOM1L1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of TOM1-like protein 1 (TOM1L1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of TOM1-like protein 1 (TOM1L1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of TOM1-like protein 1 (TOM1L1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of TOM1-like protein 1 (TOM1L1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of TOM1-like protein 1 (TOM1L1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of TOM1-like protein 1 (TOM1L1).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of TOM1-like protein 1 (TOM1L1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of TOM1-like protein 1 (TOM1L1).	[13]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of TOM1-like protein 1 (TOM1L1).	[15]

2 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 decreases the methylation of TOM1-like protein 1 (TOM1L1).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of TOM1-like protein 1 (TOM1L1).	[14]

References

• [1] Decreased Srcasm expression in esophageal squamous cell carcinoma in a Chinese population.Anticancer Res. 2010 Sep;30(9):3535-9.
• [2] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [3] Srcasm inhibits Fyn-induced cutaneous carcinogenesis with modulation of Notch1 and p53.Cancer Res. 2009 Dec 15;69(24):9439-47. doi: 10.1158/0008-5472.CAN-09-2976.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.