Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL2KPRO)

• DOT Name: RILP-like protein 2 (RILPL2)
• Synonyms: Rab-interacting lysosomal protein-like 2; p40phox-binding protein
• Gene Name: RILPL2
• Related Disease:
  Peripheral arterial disease
  Breast cancer
  Breast carcinoma
• UniProt ID: RIPL2_HUMAN
• PDB ID: 6RIR; 6SQ2; 7LWB
• Pfam ID: PF11461
• Sequence:
  MEEPPVREEEEEEGEEDEERDEVGPEGALGKSPFQLTAEDVYDISYLLGRELMALGSDPR
  VTQLQFKVVRVLEMLEALVNEGSLALEELKMERDHLRKEVEGLRRQSPPASGEVNLGPNK
  MVVDLTDPNRPRFTLQELRDVLQERNKLKSQLLVVQEELQCYKSGLIPPREGPGGRREKD
  AVVTSAKNAGRNKEEKTIIKKLFFFRSGKQT
• Function: Involved in cell shape and neuronal morphogenesis, positively regulating the establishment and maintenance of dendritic spines. Plays a role in cellular protein transport, including protein transport away from primary cilia. May function via activation of RAC1 and PAK1.
• Tissue Specificity: Widely expressed. Expressed at higher level in lung.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]

12 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 RILP-like protein 2 (RILPL2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RILP-like protein 2 (RILPL2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RILP-like protein 2 (RILPL2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of RILP-like protein 2 (RILPL2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of RILP-like protein 2 (RILPL2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RILP-like protein 2 (RILPL2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RILP-like protein 2 (RILPL2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of RILP-like protein 2 (RILPL2).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RILP-like protein 2 (RILPL2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of RILP-like protein 2 (RILPL2).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RILP-like protein 2 (RILPL2).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of RILP-like protein 2 (RILPL2).	[14]

References

• [1] Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.PLoS One. 2016 Apr 15;11(4):e0152670. doi: 10.1371/journal.pone.0152670. eCollection 2016.
• [2] RILPL2 regulates breast cancer proliferation, metastasis, and chemoresistance via the TUBB3/PTEN pathway.Am J Cancer Res. 2019 Aug 1;9(8):1583-1606. eCollection 2019.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.