Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8YLN94)

• DOT Name: Actin-binding LIM protein 3 (ABLIM3)
• Synonyms: abLIM-3; Actin-binding LIM protein family member 3
• Gene Name: ABLIM3
• UniProt ID: ABLM3_HUMAN
• PDB ID: 1UJS; 2DJ7
• Pfam ID: PF16182 ; PF00412 ; PF02209
• Sequence:
  MNTSIPYQQNPYNPRGSSNVIQCYRCGDTCKGEVVRVHNNHFHIRCFTCQVCGCGLAQSG
  FFFKNQEYICTQDYQQLYGTRCDSCRDFITGEVISALGRTYHPKCFVCSLCRKPFPIGDK
  VTFSGKECVCQTCSQSMASSKPIKIRGPSHCAGCKEEIKHGQSLLALDKQWHVSCFKCQT
  CSVILTGEYISKDGVPYCESDYHAQFGIKCETCDRYISGRVLEAGGKHYHPTCARCVRCH
  QMFTEGEEMYLTGSEVWHPICKQAARAEKKLKHRRTSETSISPPGSSIGSPNRVICAKVD
  NEILNYKDLAALPKVKSIYEVQRPDLISYEPHSRYMSDEMLERCGYGESLGTLSPYSQDI
  YENLDLRQRRASSPGYIDSPTYSRQGMSPTFSRSPHHYYRSGPESGRSSPYHSQLDVRSS
  TPTSYQAPKHFHIPAGDSNIYRKPPIYKRHGDLSTATKSKTSEDISQTSKYSPIYSPDPY
  YASESEYWTYHGSPKVPRARRFSSGGEEDDFDRSMHKLQSGIGRLILKEEMKARSSSYAD
  PWTPPRSSTSSREALHTAGYEMSLNGSPRSHYLADSDPLISKSASLPAYRRNGLHRTPSA
  DLFHYDSMNAVNWGMREYKIYPYELLLVTTRGRNRLPKDVDRTRLERHLSQEEFYQVFGM
  TISEFDRLALWKRNELKKQARLF
• Function: May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity.
• Tissue Specificity: Expressed predominantly in heart and brain.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway: DCC mediated attractive signaling (R-HSA-418885)

Molecular Interaction Atlas (MIA) of This DOT

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Actin-binding LIM protein 3 (ABLIM3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Actin-binding LIM protein 3 (ABLIM3).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Actin-binding LIM protein 3 (ABLIM3).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Actin-binding LIM protein 3 (ABLIM3).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Actin-binding LIM protein 3 (ABLIM3).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Actin-binding LIM protein 3 (ABLIM3).	[14]

1 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 Actin-binding LIM protein 3 (ABLIM3).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] 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.
• [7] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.