Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT90BA3B)

• DOT Name: Synembryn-B (RIC8B)
• Synonyms: Brain synembryn; hSyn; Protein Ric-8B
• Gene Name: RIC8B
• UniProt ID: RIC8B_HUMAN
• Pfam ID: PF10165
• Sequence:
  MDEERALYIVRAGEAGAIERVLRDYSDKHRATFKFESTDEDKRKKLCEGIFKVLIKDIPT
  TCQVSCLEVLRILSRDKKVLVPVTTKENMQILLRLAKLNELDDSLEKVSEFPVIVESLKC
  LCNIVFNSQMAQQLSLELNLAAKLCNLLRKCKDRKFINDIKCFDLRLLFLLSLLHTDIRS
  QLRYELQGLPLLTQILESAFSIKWTDEYESAIDHNGPPLSPQETDCAIEALKALFNVTVD
  SWKVHKESDSHQFRVMAAVLRHCLLIVGPTEDKTEELHSNAVNLLSNVPVSCLDVLICPL
  THEETAQEATTLDELPSNKTAEKETVLKNNTMVYNGMNMEAIHVLLNFMEKRIDKGSSYR
  EGLTPVLSLLTECSRAHRNIRKFLKDQVLPPLRDVTNRPEVGSTVRNKLVRLMTHVDLGV
  KQIAAEFLFVLCKERVDSLLKYTGYGNAAGLLAARGLLAGGRGDNWYSEDEDTDTEEYKN
  AKPKEELLKPMGLKPDGTITPLEEALNQYSVIEETSSDTD
• Function: Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins by exchanging bound GDP for free GTP. Able to potentiate G(olf)-alpha-dependent cAMP accumulation suggesting that it may be an important component for odorant signal transduction.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Synembryn-B (RIC8B).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Synembryn-B (RIC8B).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Synembryn-B (RIC8B).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synembryn-B (RIC8B).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Synembryn-B (RIC8B).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Synembryn-B (RIC8B).	[4]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Synembryn-B (RIC8B).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Synembryn-B (RIC8B).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Synembryn-B (RIC8B).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synembryn-B (RIC8B).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Synembryn-B (RIC8B).	[11]

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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] 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.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] 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.