Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSSP13W)

• DOT Name: Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2)
• Gene Name: ITPRIPL2
• UniProt ID: IPIL2_HUMAN
• Pfam ID: PF20266
• Sequence:
  MSVHYTLNLRVFWPLVTGLCTALVCLYHVLRGSGGARAEPADGVDGGFPLLKVAVLLLLS
  YVLLRCRHAVRQRFLPGSPRLEGHAAFSSRHFREPGLSILLESYYEHEVRLSPHVLGHSK
  AHVSRIVGELVRAGRARGSPGLIPGGALALAFRGDFIQVGSAYEQHKIRRPDSFDVLVPL
  RLPPLVALEPRSLGEEPALAPAFRGCFLCALKAPPSPSGASGGHWLRDCKPFADAFCVDV
  RGRRHLSATLVLRWFQSHLQRSLATVRYSLEGRCRVTLTPGGLEQPPTLHILPCRTDYGC
  CRLSMAVRLIPAVHLGDGVFLVAPPPPPLPSAPLLELPEGLRAEALWGVNTARQEQKLLS
  WLQERAAPGACYLKCLQLLKALRDLGARGLDSAAATQWGRILSSYVLKTVLLAVLLRKGA
  PGQGWDEEHLGRCLEELVQFLRDCLLRRHTLFHCVLGPGGAAAEVGPLPKALREAAPVDL
  LAAFDGHARELAAARLLSTWQRLPQLLRAYGGPRYLARCPPPRSQRTQGFLEGEP

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[1]

14 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 Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Inositol 1,4,5-trisphosphate receptor-interacting protein-like 2 (ITPRIPL2).	[14]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 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] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [10] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.