Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4V9SRK)

• DOT Name: Ras association domain-containing protein 3 (RASSF3)
• Gene Name: RASSF3
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Familial prostate carcinoma
  Head-neck squamous cell carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Lung adenocarcinoma
• UniProt ID: RASF3_HUMAN
• Pfam ID: PF16517 ; PF00788
• Sequence:
  MSSGYSSLEEDAEDFFFTARTSFFRRAPQGKPRSGQQDVEKEKETHSYLSKEEIKEKVHK
  YNLAVTDKLKMTLNSNGIYTGFIKVQMELCKPPQTSPNSGKLSPSSNGCMNTLHISSTNT
  VGEVIEALLKKFLVTESPAKFALYKRCHREDQVYACKLSDREHPLYLRLVAGPRTDTLSF
  VLREHEIGEWEAFSLPELQNFLRILDKEEDEQLQNLKRRYTAYRQKLEEALREVWKPD
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[3]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[3]
Lung adenocarcinoma	DISD51WR	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ras association domain-containing protein 3 (RASSF3).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras association domain-containing protein 3 (RASSF3).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Ras association domain-containing protein 3 (RASSF3).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ras association domain-containing protein 3 (RASSF3).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Ras association domain-containing protein 3 (RASSF3).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ras association domain-containing protein 3 (RASSF3).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras association domain-containing protein 3 (RASSF3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ras association domain-containing protein 3 (RASSF3).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ras association domain-containing protein 3 (RASSF3).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras association domain-containing protein 3 (RASSF3).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Ras association domain-containing protein 3 (RASSF3).	[15]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Ras association domain-containing protein 3 (RASSF3).	[16]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Ras association domain-containing protein 3 (RASSF3).	[17]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ras association domain-containing protein 3 (RASSF3).	[14]

References

• [1] RASSF3 downregulation increases malignant phenotypes of non-small cell lung cancer.Lung Cancer. 2014 Jan;83(1):23-9. doi: 10.1016/j.lungcan.2013.10.014. Epub 2013 Oct 31.
• [2] Rassf3 is responsible in part for resistance to mammary tumor development in neu transgenic mice.Int J Oncol. 2009 Feb;34(2):517-28.
• [3] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [4] Functional single nucleotide polymorphisms of the RASSF3 gene and susceptibility to squamous cell carcinoma of the head and neck.Eur J Cancer. 2014 Feb;50(3):582-92. doi: 10.1016/j.ejca.2013.11.009. Epub 2013 Nov 29.
• [5] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] 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.
• [17] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.