Details of Drug Off-Target (DOT)

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

• DOT Name: Endosialin (CD248)
• Synonyms: Tumor endothelial marker 1; CD antigen CD248
• Gene Name: CD248
• UniProt ID: CD248_HUMAN
• Pfam ID: PF14670 ; PF00059
• Sequence:
  MLLRLLLAWAAAGPTLGQDPWAAEPRAACGPSSCYALFPRRRTFLEAWRACRELGGDLAT
  PRTPEEAQRVDSLVGAGPASRLLWIGLQRQARQCQLQRPLRGFTWTTGDQDTAFTNWAQP
  ASGGPCPAQRCVALEASGEHRWLEGSCTLAVDGYLCQFGFEGACPALQDEAGQAGPAVYT
  TPFHLVSTEFEWLPFGSVAAVQCQAGRGASLLCVKQPEGGVGWSRAGPLCLGTGCSPDNG
  GCEHECVEEVDGHVSCRCTEGFRLAADGRSCEDPCAQAPCEQQCEPGGPQGYSCHCRLGF
  RPAEDDPHRCVDTDECQIAGVCQQMCVNYVGGFECYCSEGHELEADGISCSPAGAMGAQA
  SQDLGDELLDDGEDEEDEDEAWKAFNGGWTEMPGILWMEPTQPPDFALAYRPSFPEDREP
  QIPYPEPTWPPPLSAPRVPYHSSVLSVTRPVVVSATHPTLPSAHQPPVIPATHPALSRDH
  QIPVIAANYPDLPSAYQPGILSVSHSAQPPAHQPPMISTKYPELFPAHQSPMFPDTRVAG
  TQTTTHLPGIPPNHAPLVTTLGAQLPPQAPDALVLRTQATQLPIIPTAQPSLTTTSRSPV
  SPAHQISVPAATQPAALPTLLPSQSPTNQTSPISPTHPHSKAPQIPREDGPSPKLALWLP
  SPAPTAAPTALGEAGLAEHSQRDDRWLLVALLVPTCVFLVVLLALGIVYCTRCGPHAPNK
  RITDCYRWVIHAGSKSPTEPMPPRGSLTGVQTCRTSV
• Function: May play a role in tumor angiogenesis.
• Tissue Specificity: Expressed in tumor endothelial cells but absent or barely detectable in normal endothelial cells. Expressed in metastatic lesions of the liver and during angiogenesis of corpus luteum formation and wound healing. Expressed in vascular endothelial cells of malignant tumors but not in normal blood vessels. Expressed in stromal fibroblasts.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Endosialin (CD248).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Endosialin (CD248).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Endosialin (CD248).	[9]

6 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 Endosialin (CD248).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Endosialin (CD248).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Endosialin (CD248).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Endosialin (CD248).	[5]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid affects the expression of Endosialin (CD248).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Endosialin (CD248).	[8]

References

• [1] 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.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
• [7] 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.
• [8] 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.
• [9] 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.