Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTINWTT9)

• DOT Name: Akirin-1 (AKIRIN1)
• Gene Name: AKIRIN1
• UniProt ID: AKIR1_HUMAN
• Sequence:
  MACGATLKRPMEFEAALLSPGSPKRRRCAPLPGPTPGLRPPDAEPPPPFQTQTPPQSLQQ
  PAPPGSERRLPTPEQIFQNIKQEYSRYQRWRHLEVVLNQSEACASESQPHSSALTAPSSP
  GSSWMKKDQPTFTLRQVGIICERLLKDYEDKIREEYEQILNTKLAEQYESFVKFTHDQIM
  RRYGTRPTSYVS
• Function: Molecular adapter that acts as a bridge between proteins, and which is involved skeletal muscle development. Functions as a signal transducer for MSTN during skeletal muscle regeneration and myogenesis. May regulate chemotaxis of both macrophages and myoblasts by reorganising actin cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase dependent pathway. In contrast to AKIRIN2, not involved in nuclear import of proteasomes.
• Tissue Specificity: Widely expressed with the highest expression in heart, liver, placenta and peripheral blood leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Akirin-1 (AKIRIN1).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Akirin-1 (AKIRIN1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Akirin-1 (AKIRIN1).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Akirin-1 (AKIRIN1).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Akirin-1 (AKIRIN1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Akirin-1 (AKIRIN1).	[8]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Akirin-1 (AKIRIN1).	[9]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Akirin-1 (AKIRIN1).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Akirin-1 (AKIRIN1).	[7]

References

• [1] 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.
• [2] 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.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] 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.
• [8] 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.
• [9] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.