Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOCY7XY)

• DOT Name: Adhesion G protein-coupled receptor B2 (ADGRB2)
• Synonyms: Brain-specific angiogenesis inhibitor 2
• Gene Name: ADGRB2
• Related Disease:
  Cerebral infarction
  Brain neoplasm
  Pathologic nystagmus
• UniProt ID: AGRB2_HUMAN
• PDB ID: 8OEK
• Pfam ID: PF00002 ; PF19188 ; PF16489 ; PF01825 ; PF00090
• Sequence:
  MENTGWMGKGHRMTPACPLLLSVILSLRLATAFDPAPSACSALASGVLYGAFSLQDLFPT
  IASGCSWTLENPDPTKYSLYLRFNRQEQVCAHFAPRLLPLDHYLVNFTCLRPSPEEAVAQ
  AESEVGRPEEEEAEAAAGLELCSGSGPFTFLHFDKNFVQLCLSAEPSEAPRLLAPAALAF
  RFVEVLLINNNNSSQFTCGVLCRWSEECGRAAGRACGFAQPGCSCPGEAGAGSTTTTSPG
  PPAAHTLSNALVPGGPAPPAEADLHSGSSNDLFTTEMRYGEEPEEEPKVKTQWPRSADEP
  GLYMAQTGDPAAEEWSPWSVCSLTCGQGLQVRTRSCVSSPYGTLCSGPLRETRPCNNSAT
  CPVHGVWEEWGSWSLCSRSCGRGSRSRMRTCVPPQHGGKACEGPELQTKLCSMAACPVEG
  QWLEWGPWGPCSTSCANGTQQRSRKCSVAGPAWATCTGALTDTRECSNLECPATDSKWGP
  WNAWSLCSKTCDTGWQRRFRMCQATGTQGYPCEGTGEEVKPCSEKRCPAFHEMCRDEYVM
  LMTWKKAAAGEIIYNKCPPNASGSASRRCLLSAQGVAYWGLPSFARCISHEYRYLYLSLR
  EHLAKGQRMLAGEGMSQVVRSLQELLARRTYYSGDLLFSVDILRNVTDTFKRATYVPSAD
  DVQRFFQVVSFMVDAENKEKWDDAQQVSPGSVHLLRVVEDFIHLVGDALKAFQSSLIVTD
  NLVISIQREPVSAVSSDITFPMRGRRGMKDWVRHSEDRLFLPKEVLSLSSPGKPATSGAA
  GSPGRGRGPGTVPPGPGHSHQRLLPADPDESSYFVIGAVLYRTLGLILPPPRPPLAVTSR
  VMTVTVRPPTQPPAEPLITVELSYIINGTTDPHCASWDYSRADASSGDWDTENCQTLETQ
  AAHTRCQCQHLSTFAVLAQPPKDLTLELAGSPSVPLVIGCAVSCMALLTLLAIYAAFWRF
  IKSERSIILLNFCLSILASNILILVGQSRVLSKGVCTMTAAFLHFFFLSSFCWVLTEAWQ
  SYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRTKGYGTSSYCWLSLEGGLLYAF
  VGPAAVIVLVNMLIGIIVFNKLMARDGISDKSKKQRAGSERCPWASLLLPCSACGAVPSP
  LLSSASARNAMASLWSSCVVLPLLALTWMSAVLAMTDRRSVLFQALFAVFNSAQGFVITA
  VHCFLRREVQDVVKCQMGVCRADESEDSPDSCKNGQLQILSDFEKDVDLACQTVLFKEVN
  TCNPSTITGTLSRLSLDEDEEPKSCLVGPEGSLSFSPLPGNILVPMAASPGLGEPPPPQE
  ANPVYMCGEGGLRQLDLTWLRPTEPGSEGDYMVLPRRTLSLQPGGGGGGGEDAPRARPEG
  TPRRAAKTVAHTEGYPSFLSVDHSGLGLGPAYGSLQNPYGMTFQPPPPTPSARQVPEPGE
  RSRTMPRTVPGSTMKMGSLERKKLRYSDLDFEKVMHTRKRHSELYHELNQKFHTFDRYRS
  QSTAKREKRWSVSSGGAAERSVCTDKPSPGERPSLSQHRRHQSWSTFKSMTLGSLPPKPR
  ERLTLHRAAAWEPTEPPDGDFQTEV
• Function: Orphan G-protein coupled receptor involved in cell adhesion and probably in cell-cell interactions. Activates NFAT-signaling pathway, a transcription factor, via the G-protein GNAZ. Involved in angiogenesis inhibition.
• Tissue Specificity: Detected in cerebrospinal fluid (at protein level) . Strongly expressed in brain. Also detected in heart, thymus, skeletal muscle, and different cell lines.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral infarction	DISR1WNP	Definitive	Altered Expression	[1]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[2]
Pathologic nystagmus	DIS1QSPO	Strong	Genetic Variation	[3]

10 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 Adhesion G protein-coupled receptor B2 (ADGRB2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[7]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Adhesion G protein-coupled receptor B2 (ADGRB2).	[12]

References

• [1] Brain-specific angiogenesis inhibitor 2 regulates VEGF through GABP that acts as a transcriptional repressor.FEBS Lett. 2006 Jan 23;580(2):669-76. doi: 10.1016/j.febslet.2005.12.086. Epub 2006 Jan 6.
• [2] Expression of brain-specific angiogenesis inhibitor 3 (BAI3) in normal brain and implications for BAI3 in ischemia-induced brain angiogenesis and malignant glioma.FEBS Lett. 2004 Jul 2;569(1-3):307-16. doi: 10.1016/j.febslet.2004.06.011.
• [3] A disease-associated mutation in the adhesion GPCR BAI2 (ADGRB2) increases receptor signaling activity.Hum Mutat. 2017 Dec;38(12):1751-1760. doi: 10.1002/humu.23336. Epub 2017 Sep 20.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [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] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [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] 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] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.