Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQNI7L8)

• DOT Name: Low-density lipoprotein receptor-related protein 11 (LRP11)
• Synonyms: LRP-11
• Gene Name: LRP11
• Related Disease: Neoplasm
• UniProt ID: LRP11_HUMAN
• Pfam ID: PF00057 ; PF07502
• Sequence:
  MASVAQESAGSQRRLPPRHGALRGLLLLCLWLPSGRAALPPAAPLSELHAQLSGVEQLLE
  EFRRQLQQERPQEELELELRAGGGPQEDCPGPGSGGYSAMPDAIIRTKDSLAAGASFLRA
  PAAVRGWRQCVAACCSEPRCSVAVVELPRRPAPPAAVLGCYLFNCTARGRNVCKFALHSG
  YSSYSLSRAPDGAALATARASPRQEKDAPPLSKAGQDVVLHLPTDGVVLDGRESTDDHAI
  VQYEWALLQGDPSVDMKVPQSGTLKLSHLQEGTYTFQLTVTDTAGQRSSDNVSVTVLRAA
  YSTGGCLHTCSRYHFFCDDGCCIDITLACDGVQQCPDGSDEDFCQNLGLDRKMVTHTAAS
  PALPRTTGPSEDAGGDSLVEKSQKATAPNKPPALSNTEKRNHSAFWGPESQIIPVMPDSS
  SSGKNRKEESYIFESKGDGGGGEHPAPETGAVLPLALGLAITALLLLMVACRLRLVKQKL
  KKARPITSEESDYLINGMYL

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[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 Low-density lipoprotein receptor-related protein 11 (LRP11).	[2]

12 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 Low-density lipoprotein receptor-related protein 11 (LRP11).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[12]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Low-density lipoprotein receptor-related protein 11 (LRP11).	[13]

References

• [1] The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer.Cancer Manag Res. 2019 Aug 30;11:8081-8093. doi: 10.2147/CMAR.S211912. eCollection 2019.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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.