Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC0IJ87)

• DOT Name: DENN domain-containing protein 11 (DENND11)
• Synonyms: DENND11; Protein LCHN
• Gene Name: DENND11
• Related Disease:
  Cerebral infarction
  Lung cancer
  Lung carcinoma
• UniProt ID: DEN11_HUMAN
• Pfam ID: PF09804
• Sequence:
  MVEQGDAAPLLRWAEGPAVSLPQAPQPQAGGWGRGGGGGARPAAEPPRRREPEEPAAPEV
  LLQPGRLELGDVEEDQVVAVFVVTFDPRSGNMVEWCLPQDIDLEGVEFKSMASGSHKIQS
  DFIYFRKGPFFGLACFANMPVESELERGARMKSVGILSPSYTLLYRYMHFLENQVRHQLE
  MPGHYSHLAAFYEDKKGVLHAGPGRGSSLPPVYWLPSIHRYMYPEMKITHPAGCMSQFIK
  FFGEQILILWKFALLRKRILIFSPPPVGVVCYRVYCCCCLANVSLPGIGGTIPESKPFFY
  VNVADIESLEVEVSYVACTTEKIFEEKRELYDVYVDNQNVKTHHDHLQPLLKINSADREK
  YRRLNEQRQMLLYSQEVEEDYNPCEEDLFVLFFLEQNNRIFQTLLEVSASQDKTLTAEHA
  RGMGLDPQGDRSFLLDLLEAYGIDVMLVIDNPCCP
• Function: Probable guanine nucleotide exchange factor (GEF). May promote the exchange of GDP to GTP, converting inactive GDP-bound small GTPases into their active GTP-bound form (Probable). May play a role in neuritogenesis, as well as in neuronal recovery and/or restructuring in the hippocampus following transient cerebral ischemia.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral infarction	DISR1WNP	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[2]
Lung carcinoma	DISTR26C	moderate	Genetic Variation	[2]

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 DENN domain-containing protein 11 (DENND11).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DENN domain-containing protein 11 (DENND11).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DENN domain-containing protein 11 (DENND11).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DENN domain-containing protein 11 (DENND11).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DENN domain-containing protein 11 (DENND11).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DENN domain-containing protein 11 (DENND11).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of DENN domain-containing protein 11 (DENND11).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of DENN domain-containing protein 11 (DENND11).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DENN domain-containing protein 11 (DENND11).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of DENN domain-containing protein 11 (DENND11).	[11]

References

• [1] Isolation and characterization of LCHN: a novel factor induced by transient global ischemia in the adult rat hippocampus.J Neurochem. 2007 Apr;101(1):263-73. doi: 10.1111/j.1471-4159.2006.04374.x.
• [2] Identification and validation of gene module associated with lung cancer through coexpression network analysis.Gene. 2015 May 25;563(1):56-62. doi: 10.1016/j.gene.2015.03.008. Epub 2015 Mar 7.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] 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.
• [9] 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.
• [10] 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.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.