Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE7K9D7)

• DOT Name: G-protein coupled receptor 157 (GPR157)
• Gene Name: GPR157
• UniProt ID: GP157_HUMAN
• Pfam ID: PF00002
• Sequence:
  MQPSPPPTELVPSERAVVLLSCALSALGSGLLVATHALWPDLRSRARRLLLFLSLADLLS
  AASYFYGVLQNFAGPSWDCVLQGALSTFANTSSFFWTVAIALYLYLSIVRAARGPRTDRL
  LWAFHVVSWGVPLVITVAAVALKKIGYDASDVSVGWCWIDLEAKDHVLWMLLTGKLWEML
  AYVLLPLLYLLVRKHINRAHTALSEYRPILSQEHRLLRHSSMADKKLVLIPLIFIGLRVW
  STVRFVLTLCGSPAVQTPVLVVLHGIGNTFQGGANCIMFVLCTRAVRTRLFSLCCCCCSS
  QPPTKSPAGTPKAPAPSKPGESQESQGTPGELPST
• Function: Orphan receptor that promotes neuronal differentiation of radial glial progenitors (RGPs). The activity of this receptor is mediated by a G(q)-protein that activates a phosphatidylinositol-calcium second messenger.

Molecular Interaction Atlas (MIA) of This DOT

2 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 G-protein coupled receptor 157 (GPR157).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of G-protein coupled receptor 157 (GPR157).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of G-protein coupled receptor 157 (GPR157).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of G-protein coupled receptor 157 (GPR157).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of G-protein coupled receptor 157 (GPR157).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of G-protein coupled receptor 157 (GPR157).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of G-protein coupled receptor 157 (GPR157).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of G-protein coupled receptor 157 (GPR157).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of G-protein coupled receptor 157 (GPR157).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of G-protein coupled receptor 157 (GPR157).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of G-protein coupled receptor 157 (GPR157).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of G-protein coupled receptor 157 (GPR157).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of G-protein coupled receptor 157 (GPR157).	[12]

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] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] 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.
• [11] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [12] 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.