Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT46I38Y)

• DOT Name: Scavenger receptor class A member 3 (SCARA3)
• Synonyms: Cellular stress response gene protein
• Gene Name: SCARA3
• Related Disease:
  Neoplasm
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Congestive heart failure
  Craniosynostosis
  Dilated cardiomyopathy 1A
  Hand, foot and mouth disease
  Lung cancer
  Lung carcinoma
  Malignant neoplasm
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Carcinoma
  Hepatocellular carcinoma
  Mesothelioma
  Primary peritoneal carcinoma
• UniProt ID: SCAR3_HUMAN
• Pfam ID: PF01391
• Sequence:
  MKVRSAGGDGDALCVTEEDLAGDDEDMPTFPCTQKGRPGPRCSRCQKNLSLHTSVRILYL
  FLALLLVAVAVLASLVFRKVDSLSEDISLTQSIYDKKLVLMQKNLQGLDPKALNNCSFCH
  EAGQLGPEIRKLQEELEGIQKLLLAQEVQLDQTLQAQEVLSTTSRQISQEMGSCSFSIHQ
  VNQSLGLFLAQVRGWQATTAGLDLSLKDLTQECYDVKAAVHQINFTVGQTSEWIHGIQRK
  TDEETLTLQKIVTDWQNYTRLFSGLRTTSTKTGEAVKNIQATLGASSQRISQNSESMHDL
  VLQVMGLQLQLDNISSFLDDHEENMHDLQYHTHYAQNRTVERFESLEGRMASHEIEIGTI
  FTNINATDNHVHSMLKYLDDVRLSCTLGFHTHAEELYYLNKSVSIMLGTTDLLRERFSLL
  SARLDLNVRNLSMIVEEMKAVDTQHGEILRNVTILRGAPGPPGPRGFKGDMGVKGPVGGR
  GPKGDPGSLGPLGPQGPQGQPGEAGPVGERGPVGPRGFPGLKGSKGSFGTGGPRGQPGPK
  GDIGPPGPEGPPGSPGPSGPQGKPGIAGKTGSPGQRGAMGPKGEPGIQGPPGLPGPPGPP
  GSQSFY
• Function: Seems to protect cells by scavenging oxidative molecules or harmful products of oxidation.
• Tissue Specificity: Expressed ubiquitously.

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Cardiac failure	DISDC067	Strong	Biomarker	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[4]
Craniosynostosis	DIS6J405	Strong	Genetic Variation	[5]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[6]
Hand, foot and mouth disease	DISKJHLL	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[8]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[8]
Malignant neoplasm	DISS6SNG	Strong	Genetic Variation	[9]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[11]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[12]
Carcinoma	DISH9F1N	moderate	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[11]
Mesothelioma	DISKWK9M	moderate	Altered Expression	[3]
Primary peritoneal carcinoma	DISKYEDV	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Scavenger receptor class A member 3 (SCARA3).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Scavenger receptor class A member 3 (SCARA3).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Scavenger receptor class A member 3 (SCARA3).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[18]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[18]
Marinol	DM70IK5	Approved	Marinol increases the expression of Scavenger receptor class A member 3 (SCARA3).	[20]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[21]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[22]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Scavenger receptor class A member 3 (SCARA3).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[26]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Scavenger receptor class A member 3 (SCARA3).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[28]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Scavenger receptor class A member 3 (SCARA3).	[29]

References

• [1] Sumoylation Negatively Regulates CSR1-Dependent Prostate Cancer Cell Death.Cell Physiol Biochem. 2018;46(5):1861-1867. doi: 10.1159/000489370. Epub 2018 Apr 25.
• [2] Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships.Breast Cancer Res. 2005;7(2):R238-47. doi: 10.1186/bcr978. Epub 2005 Jan 14.
• [3] SCARA3 mRNA is overexpressed in ovarian carcinoma compared with breast carcinoma effusions.Hum Pathol. 2012 May;43(5):669-74. doi: 10.1016/j.humpath.2011.06.003. Epub 2011 Aug 19.
• [4] Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure.Sleep. 2019 Apr 1;42(4):zsy262. doi: 10.1093/sleep/zsy262.
• [5] FGFR2 mutation in 46,XY sex reversal with craniosynostosis.Hum Mol Genet. 2015 Dec 1;24(23):6699-710. doi: 10.1093/hmg/ddv374. Epub 2015 Sep 11.
• [6] Association between polymorphisms of the HSPB7 gene and Cheyne-Stokes respiration with central sleep apnea in patients with dilated cardiomyopathy and congestive heart failure.Int J Cardiol. 2016 Oct 15;221:926-31. doi: 10.1016/j.ijcard.2016.07.107. Epub 2016 Jul 9.
• [7] Scavenger receptor class a, member 3 is associated with severity of hand, foot, and mouth disease in a case-control study.Medicine (Baltimore). 2019 Oct;98(40):e17471. doi: 10.1097/MD.0000000000017471.
• [8] Cellular processes of v-Src transformation revealed by gene profiling of primary cells--implications for human cancer.BMC Cancer. 2010 Feb 12;10:41. doi: 10.1186/1471-2407-10-41.
• [9] Two-Dimensional Speckle Tracking Echocardiography-Derived Strain Measurements in Survivors of Childhood Cancer on Angiotensin Converting Enzyme Inhibition or Receptor Blockade.Pediatr Cardiol. 2018 Oct;39(7):1404-1412. doi: 10.1007/s00246-018-1910-z. Epub 2018 May 22.
• [10] Scavenger receptor class A member 3 (SCARA3) in disease progression and therapy resistance in multiple myeloma.Leuk Res. 2013 Aug;37(8):963-9. doi: 10.1016/j.leukres.2013.03.004. Epub 2013 Mar 26.
• [11] CSR1 suppresses tumor growth and metastasis of human hepatocellular carcinoma via inhibition of HPIP.Eur Rev Med Pharmacol Sci. 2017 Oct;21(17):3813-3820.
• [12] CSR1 suppresses tumor growth and metastasis of prostate cancer.Am J Pathol. 2006 Feb;168(2):597-607. doi: 10.2353/ajpath.2006.050620.
• [13] 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.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
• [16] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [17] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [18] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [19] Selenite reactivates silenced genes by modifying DNA methylation and histones in prostate cancer cells. Carcinogenesis. 2008 Nov;29(11):2175-81.
• [20] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [21] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [22] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [25] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [26] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [27] The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells. Neurotoxicology. 2009 May;30(3):368-76.
• [28] Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
• [29] Changes in differential gene expression in fibroblast cells from patients with triple A syndrome under oxidative stress. Horm Metab Res. 2013 Feb;45(2):102-8.