Details of Drug Off-Target (DOT)

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

• DOT Name: Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1)
• Synonyms: Dual specificity phosphatase inhibitor MK-STYX; Dual specificity protein phosphatase 24; Inactive dual specificity protein phosphatase MK-STYX; Map kinase phosphatase-like protein MK-STYX
• Gene Name: STYXL1
• Related Disease:
  Glioblastoma multiforme
  Glioma
• UniProt ID: STYL1_HUMAN
• Pfam ID: PF00782 ; PF00581
• Sequence:
  MPGLLLCEPTELYNILNQATKLSRLTDPNYLCLLDVRSKWEYDESHVITALRVKKKNNEY
  LLPESVDLECVKYCVVYDNNSSTLEILLKDDDDDSDSDGDGKDLVPQAAIEYGRILTRLT
  HHPVYILKGGYERFSGTYHFLRTQKIIWMPQELDAFQPYPIEIVPGKVFVGNFSQACDPK
  IQKDLKIKAHVNVSMDTGPFFAGDADKLLHIRIEDSPEAQILPFLRHMCHFIEIHHHLGS
  VILIFSTQGISRSCAAIIAYLMHSNEQTLQRSWAYVKKCKNNMCPNRGLVSQLLEWEKTI
  LGDSITNIMDPLY
• Function: Catalytically inactive phosphatase. By binding to G3BP1, inhibits the formation of G3BP1-induced stress granules. Does not act by protecting the dephosphorylation of G3BP1 at 'Ser-149'. Inhibits PTPMT1 phosphatase activity. By inhibiting PTPMT1, positively regulates intrinsic apoptosis. May play a role in the formation of neurites during neuronal development.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1) decreases the response to substance of Camptothecin.	[10]

9 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 Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1).	[9]

References

• [1] Serine/threonine/tyrosine-interacting-like protein 1 (STYXL1), a pseudo phosphatase, promotes oncogenesis in glioma.Biochem Biophys Res Commun. 2019 Jul 12;515(1):241-247. doi: 10.1016/j.bbrc.2019.05.093. Epub 2019 May 27.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.