Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHANJ7A)

• DOT Name: Macrophage scavenger receptor types I and II (MSR1)
• Synonyms: Macrophage acetylated LDL receptor I and II; Scavenger receptor class A member 1; CD antigen CD204
• Gene Name: MSR1
• Related Disease: Barrett esophagus
• UniProt ID: MSRE_HUMAN
• PDB ID: 7DPX
• Pfam ID: PF01391 ; PF03523 ; PF00530
• Sequence:
  MEQWDHFHNQQEDTDSCSESVKFDARSMTALLPPNPKNSPSLQEKLKSFKAALIALYLLV
  FAVLIPLIGIVAAQLLKWETKNCSVSSTNANDITQSLTGKGNDSEEEMRFQEVFMEHMSN
  MEKRIQHILDMEANLMDTEHFQNFSMTTDQRFNDILLQLSTLFSSVQGHGNAIDEISKSL
  ISLNTTLLDLQLNIENLNGKIQENTFKQQEEISKLEERVYNVSAEIMAMKEEQVHLEQEI
  KGEVKVLNNITNDLRLKDWEHSQTLRNITLIQGPPGPPGEKGDRGPTGESGPRGFPGPIG
  PPGLKGDRGAIGFPGSRGLPGYAGRPGNSGPKGQKGEKGSGNTLTPFTKVRLVGGSGPHE
  GRVEILHSGQWGTICDDRWEVRVGQVVCRSLGYPGVQAVHKAAHFGQGTGPIWLNEVFCF
  GRESSIEECKIRQWGTRACSHSEDAGVTCTL
• Function: Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL). Isoform III does not internalize acetylated LDL.
• Tissue Specificity: Isoform I, isoform II and isoform III are expressed in monocyte-derived macrophages. Isoform I and isoform II are expressed in the liver, placenta and brain.
• KEGG Pathway: Phagosome (hsa04145)
• Reactome Pathway: Scavenging by Class A Receptors (R-HSA-3000480)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Barrett esophagus	DIS416Y7	Limited	Unknown	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Macrophage scavenger receptor types I and II (MSR1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Macrophage scavenger receptor types I and II (MSR1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Macrophage scavenger receptor types I and II (MSR1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Macrophage scavenger receptor types I and II (MSR1).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Macrophage scavenger receptor types I and II (MSR1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Macrophage scavenger receptor types I and II (MSR1).	[5]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Macrophage scavenger receptor types I and II (MSR1).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Macrophage scavenger receptor types I and II (MSR1).	[7]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Macrophage scavenger receptor types I and II (MSR1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Macrophage scavenger receptor types I and II (MSR1).	[11]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Macrophage scavenger receptor types I and II (MSR1).	[12]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [7] Resveratrol regulates the expression of LXR-alpha in human macrophages. Biochem Biophys Res Commun. 2006 Sep 29;348(3):1047-54. doi: 10.1016/j.bbrc.2006.07.155. Epub 2006 Aug 1.
• [8] Synthetic retinoid Am80 reduces scavenger receptor expression and atherosclerosis in mice by inhibiting IL-6. Arterioscler Thromb Vasc Biol. 2006 May;26(5):1177-83. doi: 10.1161/01.ATV.0000214296.94849.1c. Epub 2006 Feb 16.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] The pharmacodynamic effects of sirolimus and sirolimus-calcineurin inhibitor combinations on macrophage scavenger and nuclear hormone receptors. J Pharm Sci. 2007 Jan;96(1):209-22. doi: 10.1002/jps.20751.