Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0Z04L6)

• DOT Name: Serine hydrolase RBBP9 (RBBP9)
• Synonyms: EC 3.-.-.-; B5T-overexpressed gene protein; Protein BOG; Retinoblastoma-binding protein 10; RBBP-10; Retinoblastoma-binding protein 9; RBBP-9
• Gene Name: RBBP9
• UniProt ID: RBBP9_HUMAN
• PDB ID: 2QS9; 7OEX
• EC Number: 3.-.-.-
• Pfam ID: PF06821
• Sequence:
  MASPSKAVIVPGNGGGDVTTHGWYGWVKKELEKIPGFQCLAKNMPDPITARESIWLPFME
  TELHCDEKTIIIGHSSGAIAAMRYAETHRVYAIVLVSAYTSDLGDENERASGYFTRPWQW
  EKIKANCPYIVQFGSTDDPFLPWKEQQEVADRLETKLHKFTDCGHFQNTEFHELITVVKS
  LLKVPA
• Function: Serine hydrolase whose substrates have not been identified yet. May negatively regulate basal or autocrine TGF-beta signaling by suppressing SMAD2-SMAD3 phosphorylation. May play a role in the transformation process due to its capacity to confer resistance to the growth-inhibitory effects of TGF-beta through interaction with RB1 and the subsequent displacement of E2F1.
• Tissue Specificity: Expressed at higher levels in tumor tissues such as carcinoma.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Serine hydrolase RBBP9 (RBBP9).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Serine hydrolase RBBP9 (RBBP9).	[6]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine hydrolase RBBP9 (RBBP9).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[10]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Serine hydrolase RBBP9 (RBBP9).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Serine hydrolase RBBP9 (RBBP9).	[13]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Serine hydrolase RBBP9 (RBBP9).	[14]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] 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.
• [7] Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [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] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [14] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.