Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHZMO8Y)

• DOT Name: Regulating synaptic membrane exocytosis protein 4 (RIMS4)
• Synonyms: RIM4 gamma; Rab3-interacting molecule 4; RIM 4
• Gene Name: RIMS4
• UniProt ID: RIMS4_HUMAN
• Pfam ID: PF00168
• Sequence:
  MERSQSRLSLSASFEALAIYFPCMNSFDDEDAGDSRRLKGAIQRSTETGLAVEMPSRTLR
  QASHESIEDSMNSYGSEGNLNYGGVCLASDAQFSDFLGSMGPAQFVGRQTLATTPMGDVE
  IGLQERNGQLEVDIIQARGLTAKPGSKTLPAAYIKAYLLENGICIAKKKTKVARKSLDPL
  YNQVLLFPESPQGKVLQVIVWGNYGRMERKQFMGVARVLLEELDLTTLAVGWYKLFPTSS
  MVDPATGPLLRQASQLSLESTVGPCGERS
• Function: Regulates synaptic membrane exocytosis.

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
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[4]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[6]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[5]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[8]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Regulating synaptic membrane exocytosis protein 4 (RIMS4).	[9]

References

• [1] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [9] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.