Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPF8W4P)

• DOT Name: CTD small phosphatase-like protein 2 (CTDSPL2)
• Synonyms: CTDSP-like 2; EC 3.1.3.-
• Gene Name: CTDSPL2
• UniProt ID: CTSL2_HUMAN
• EC Number: 3.1.3.-
• Pfam ID: PF03031
• Sequence:
  MRLRTRKASQQSNQIQTQRTARAKRKYSEVDDSLPSGGEKPSKNETGLLSSIKKFIKGST
  PKEERENPSKRSRIERDIDNNLITSTPRAGEKPNKQISRVRRKSQVNGEAGSYEMTNQHV
  KQNGKLEDNPSSGSPPRTTLLGTIFSPVFNFFSPANKNGTSGSDSPGQAVEAEEIVKQLD
  MEQVDEITTSTTTSTNGAAYSNQAVQVRPSLNNGLEEAEETVNRDIPPLTAPVTPDSGYS
  SAHAEATYEEDWEVFDPYYFIKHVPPLTEEQLNRKPALPLKTRSTPEFSLVLDLDETLVH
  CSLNELEDAALTFPVLFQDVIYQVYVRLRPFFREFLERMSQMYEIILFTASKKVYADKLL
  NILDPKKQLVRHRLFREHCVCVQGNYIKDLNILGRDLSKTIIIDNSPQAFAYQLSNGIPI
  ESWFMDKNDNELLKLIPFLEKLVELNEDVRPHIRDRFRLHDLLPPD
• Function: Probable phosphatase.

Molecular Interaction Atlas (MIA) of This DOT

15 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 CTD small phosphatase-like protein 2 (CTDSPL2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[10]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[8]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[16]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of CTD small phosphatase-like protein 2 (CTDSPL2).	[17]

3 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 CTD small phosphatase-like protein 2 (CTDSPL2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of CTD small phosphatase-like protein 2 (CTDSPL2).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of CTD small phosphatase-like protein 2 (CTDSPL2).	[15]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] 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.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] 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.
• [12] 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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [15] 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.
• [16] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [17] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.