Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKV8BMJ)

• DOT Name: RPA-related protein RADX (RADX)
• Synonyms: RPA-related and RAD51-antagonist, X-chromosome
• Gene Name: RADX
• UniProt ID: RADX_HUMAN
• PDB ID: 8U5Y
• Pfam ID: PF17659
• Sequence:
  MSGESGQPEAGPSHAGLDWPNPERNRAGVPGGVIRRAGSQGPRSWIQKVLEQIMDSPRQC
  VTPSEVVPVTVLAVQRYLLEDEPRDTVPKPPLYCYDVTISDGVYQEKCYLDPSLNSLVYQ
  NILKVGIQMRISRVSCLYNEKRIGQGILCIDNVHCGETSDSISLETPFRNRAHQEKPERP
  LRGGKSHYLALWNNEDPYGDIWLTDKQPEEHNFSDTKIISLSHLEMTWTNRRNFPALLVR
  ILHKSKLRYYGKPDKKMIEPYQTFLEVADSSGTVSVIMWNALCPEWYKSLRVGLVLLLQD
  YSVKKSYPFRIQPVPVDPQIKLISTMEICLNLRDPPTNIIIIPEKQVKPEWRLPKLNHRF
  TTRSELDDMPENCICDVIGLLVFVGRVQRSKKKENREDFWSYRWIHIADGTSEQPFIVEL
  FSTSQPEIFENIYPMAYFVCTQLKVVRNDNQVPKLLYLTTTNESGVFITGHRGQPYTYDA
  KVKNFIQWIRTKSDSGEQKNMVIGGYYPYPPVPETFSKYSSSIKVESLLTAISEVRKEIE
  DLQYREQKRIAIQGIITAIKYIPHSSATESASASETLRNANRPSTSQAARVEIQERNGKR
  HQDDEPVNSQYFQTTSTNLSLSNKIRILQGPHANPVAVPQPGASVQTKGIKPGMPSIFNR
  RANINANLQGKARKTISDRWESQLWREKKFGLIDHLHYSRVYPESIPRKFMFEHRKFLSD
  QYNSQPAKYVPPEGRPPKLDDFKSARSLGHFEVTILGLNHEIAIDVAFLPMYCPEDIRTS
  QIDTLLTSMNYSCAYPQDTTGNDRLPGPRAVAGDIIKAATELDRVHIVGILDICNLGNNK
  VEVYLHKIYSPENTS
• Function: Single-stranded DNA-binding protein recruited to replication forks to maintain genome stability. Prevents fork collapse by antagonizing the accumulation of RAD51 at forks to ensure the proper balance of fork remodeling and protection without interfering with the capacity of cells to complete homologous recombination of double-strand breaks.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of RPA-related protein RADX (RADX).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of RPA-related protein RADX (RADX).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of RPA-related protein RADX (RADX).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RPA-related protein RADX (RADX).	[2]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of RPA-related protein RADX (RADX).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of RPA-related protein RADX (RADX).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of RPA-related protein RADX (RADX).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of RPA-related protein RADX (RADX).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of RPA-related protein RADX (RADX).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of RPA-related protein RADX (RADX).	[9]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of RPA-related protein RADX (RADX).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RPA-related protein RADX (RADX).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of RPA-related protein RADX (RADX).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of RPA-related protein RADX (RADX).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of RPA-related protein RADX (RADX).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of RPA-related protein RADX (RADX).	[16]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of RPA-related protein RADX (RADX).	[4]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] 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.
• [4] 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.
• [5] 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.
• [6] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [7] 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.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [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] 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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] 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.
• [16] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.