Details of Drug Off-Target (DOT)

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

• DOT Name: Spindlin interactor and repressor of chromatin-binding protein (SPINDOC)
• Synonyms: SPIN1-docking protein; SPIN-DOC
• Gene Name: SPINDOC
• UniProt ID: SPNDC_HUMAN
• PDB ID: 7CNA; 7E9M; 7EA1
• Pfam ID: PF18658
• Sequence:
  MALKAEGAALDCFEVTLKCEEGEDEEEAMVVAVIPRPEPMLRVTQQEKTPPPRPSPLEAG
  SDGCEEPKQQVSWEQEFLVGSSPGGSGRALCMVCGAEIRAPSADTARSHILEQHPHTLDL
  SPSEKSNILEAWSEGVALLQDVRAEQPSPPNSDSGQDAHPDPDANPDAARMPAEIVVLLD
  SEDNPSLPKRSRPRGLRPLELPAVPATEPGNKKPRGQRWKEPPGEEPVRKKRGRPMTKNL
  DPDPEPPSPDSPTETFAAPAEVRHFTDGSFPAGFVLQLFSHTQLRGPDSKDSPKDREVAE
  GGLPRAESPSPAPPPGLRGTLDLQVIRVRMEEPPAVSLLQDWSRHPQGTKRVGAGDTSDW
  PTVLSESSTTVAGKPEKGNGV
• Function: Negatively regulates the transcriptional activator activity of SPIN1 via inhibition of its histone methyl-binding ability. Represses the expression of a number of SPIN1-regulated genes and the SPIN1-mediated activation of the Wnt signaling pathway. Can also inhibit the histone methyl-binding abilities of SPIN2A, SPIN2B, SPIN3 and SPIN4. Positively regulates poly-ADP-ribosylation in response to DNA damage; acts by facilitating PARP1 ADP-ribosyltransferase activity.

Molecular Interaction Atlas (MIA) of This DOT

5 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 Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[4]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[5]

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 decreases the methylation of Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Spindlin interactor and repressor of chromatin-binding protein (SPINDOC).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [6] 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.
• [7] 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.