Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX54ILM)

• DOT Name: Rhomboid domain-containing protein 2 (RHBDD2)
• Gene Name: RHBDD2
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Colorectal carcinoma
  Neoplasm
• UniProt ID: RHBD2_HUMAN
• Pfam ID: PF01694
• Sequence:
  MAASGPGCRSWCLCPEVPSATFFTALLSLLVSGPRLFLLQQPLAPSGLTLKSEALRNWQV
  YRLVTYIFVYENPISLLCGAIIIWRFAGNFERTVGTVRHCFFTVIFAIFSAIIFLSFEAV
  SSLSKLGEVEDARGFTPVAFAMLGVTTVRSRMRRALVFGMVVPSVLVPWLLLGASWLIPQ
  TSFLSNVCGLSIGLAYGLTYCYSIDLSERVALKLDQTFPFSLMRRISVFKYVSGSSAERR
  AAQSRKLNPVPGSYPTQSCHPHLSPSHPVSQTQHASGQKLASWPSCTPGHMPTLPPYQPA
  SGLCYVQNHFGPNPTSSSVYPASAGTSLGIQPPTPVNSPGTVYSGALGTPGAAGSKESSR
  VPMP

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]

11 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 Rhomboid domain-containing protein 2 (RHBDD2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Rhomboid domain-containing protein 2 (RHBDD2).	[13]

References

• [1] Spatiotemporal expression of Rhomboid domain containing 2 (Rhbdd2) during rat development.Acta Histochem. 2015 Sep;117(7):635-41. doi: 10.1016/j.acthis.2015.06.005. Epub 2015 Jun 18.
• [2] Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression.Oncol Rep. 2018 Aug;40(2):909-915. doi: 10.3892/or.2018.6489. Epub 2018 Jun 14.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] 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.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.