Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO2D8S0)

• DOT Name: Serum amyloid A-1 protein (SAA1)
• Synonyms: SAA
• Gene Name: SAA1
• UniProt ID: SAA1_HUMAN
• PDB ID: 4IP8; 4IP9; 6MST; 7ZKY
• Pfam ID: PF00277
• Sequence:
  MKLLTGLVFCSLVLGVSSRSFFSFLGEAFDGARDMWRAYSDMREANYIGSDKYFHARGNY
  DAAKRGPGGAWAAEVITDARENIQRFFGHGAEDSLADQAANEWGRSGKDPNHFRPAGLPE
  KY
• Function: Major acute phase protein.
• Tissue Specificity: Expressed by the liver; secreted in plasma (at protein level).
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (i) signalling events (R-HSA-418594)
  Formyl peptide receptors bind formyl peptides and many other ligands (R-HSA-444473)
  TAK1-dependent IKK and NF-kappa-B activation (R-HSA-445989)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Advanced glycosylation endproduct receptor signaling (R-HSA-879415)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  Amyloid fiber formation (R-HSA-977225)
  Scavenging by Class B Receptors (R-HSA-3000471)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serum amyloid A-1 protein (SAA1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serum amyloid A-1 protein (SAA1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serum amyloid A-1 protein (SAA1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Serum amyloid A-1 protein (SAA1).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Serum amyloid A-1 protein (SAA1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serum amyloid A-1 protein (SAA1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Serum amyloid A-1 protein (SAA1).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Serum amyloid A-1 protein (SAA1).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Serum amyloid A-1 protein (SAA1).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Serum amyloid A-1 protein (SAA1).	[9]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Serum amyloid A-1 protein (SAA1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serum amyloid A-1 protein (SAA1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serum amyloid A-1 protein (SAA1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Serum amyloid A-1 protein (SAA1).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Serum amyloid A-1 protein (SAA1).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Serum amyloid A-1 protein (SAA1).	[15]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Serum amyloid A-1 protein (SAA1).	[16]

References

• [1] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [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] Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells. Toxicol Sci. 2000 Dec;58(2):399-415.
• [4] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [5] Unique signatures of stress-induced senescent human astrocytes. Exp Neurol. 2020 Dec;334:113466. doi: 10.1016/j.expneurol.2020.113466. Epub 2020 Sep 17.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] 5-Fluorouracil up-regulates interferon pathway gene expression in esophageal cancer cells. Anticancer Res. 2005 Sep-Oct;25(5):3271-8.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [11] Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
• [12] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] 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.