Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3I0A91)

• DOT Name: Ligand of Numb protein X 2 (LNX2)
• Synonyms: Numb-binding protein 2; PDZ domain-containing RING finger protein 1
• Gene Name: LNX2
• Related Disease:
  Adult lymphoma
  Colorectal carcinoma
  Lymphoma
  Pediatric lymphoma
• UniProt ID: LNX2_HUMAN
• PDB ID: 2VWR; 5DIN; 5E11; 5E1Y; 5E21; 5E22; 7QCT
• Pfam ID: PF00595 ; PF13923
• Sequence:
  MGTTSDEMVSVEQTSSSSLNPLCFECGQQHWTRENHLYNYQNEVDDDLVCHICLQPLLQP
  LDTPCGHTFCYKCLRNFLQEKDFCPLDRKRLHFKLCKKSSILVHKLLDKLLVLCPFSSVC
  KDVMQRCDLEAHLKNRCPGASHRRVALERRKTSRTQAEIENENGPTLLDPAGTLSPEADC
  LGTGAVPVERHLTSASLSTWSEEPGLDNPAFEESAGADTTQQPLSLPEGEITTIEIHRSN
  PYIQLGISIVGGNETPLINIVIQEVYRDGVIARDGRLLAGDQILQVNNYNISNVSHNYAR
  AVLSQPCNTLHLTVLRERRFGNRAHNHSDSNSPREEIFQVALHKRDSGEQLGIKLVRRTD
  EPGVFILDLLEGGLAAQDGRLSSNDRVLAINGHDLKYGTPELAAQIIQASGERVNLTIAR
  PGKPQPGNTIREAGNHSSSSQHHTPPPYYSRPSSHKDLTQCVTCQEKHITVKKEPHESLG
  MTVAGGRGSKSGELPIFVTSVPPHGCLARDGRIKRGDVLLNINGIDLTNLSHSEAVAMLK
  ASAASPAVALKALEVQIVEEATQNAEEQPSTFSENEYDASWSPSWVMWLGLPSTLHSCHD
  IVLRRSYLGSWGFSIVGGYEENHTNQPFFIKTIVLGTPAYYDGRLKCGDMIVAVNGLSTV
  GMSHSALVPMLKEQRNKVTLTVICWPGSLV

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[1]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[1]

1 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 Ligand of Numb protein X 2 (LNX2).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ligand of Numb protein X 2 (LNX2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ligand of Numb protein X 2 (LNX2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ligand of Numb protein X 2 (LNX2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ligand of Numb protein X 2 (LNX2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ligand of Numb protein X 2 (LNX2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Ligand of Numb protein X 2 (LNX2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ligand of Numb protein X 2 (LNX2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Ligand of Numb protein X 2 (LNX2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ligand of Numb protein X 2 (LNX2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ligand of Numb protein X 2 (LNX2).	[13]

References

• [1] Common variants on 14q32 and 13q12 are associated with DLBCL susceptibility.J Hum Genet. 2011 Jun;56(6):436-9. doi: 10.1038/jhg.2011.35. Epub 2011 Apr 7.
• [2] Genetic amplification of the NOTCH modulator LNX2 upregulates the WNT/-catenin pathway in colorectal cancer.Cancer Res. 2013 Mar 15;73(6):2003-13. doi: 10.1158/0008-5472.CAN-12-3159. Epub 2013 Jan 14.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.