Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0KDWZN)

• DOT Name: Melanoma-associated antigen C3 (MAGEC3)
• Synonyms: Cancer/testis antigen 7.2; CT7.2; Hepatocellular carcinoma-associated antigen 2; MAGE-C3 antigen
• Gene Name: MAGEC3
• Related Disease:
  Infantile malignant osteopetrosis
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Metabolic bone disease
  Metastatic malignant neoplasm
  Non-insulin dependent diabetes
  Obesity
  Autosomal recessive osteopetrosis 3
  Diabetic retinopathy
  Retinopathy
  Glaucoma/ocular hypertension
  Leiomyoma
  Neoplasm
  Uterine fibroids
• UniProt ID: MAGC3_HUMAN
• Sequence:
  MLLPCHWVLDATFSDGSLGQWVKNTCATYALSPVVLPPQPQPRKKATDKDYSAFHLGHLR
  EVRLFLRGGTSDQRMDSLVLCPTYFKLWRTLSGSPGLQLSDLHFGSQPEGKFSLRRAVSV
  KQREEPQDWPLNEKRTLWKDSDLPTWRRGTGYTLSLPAVSPGKRLWGEKAGSLPESEPLF
  TYTLDEKVDKLVQFLLLKYQAKEPLTRAEMQMNVINTYTGYFPMIFRKAREFIEILFGIS
  LTEVDPDHFYVFVNTLDLTCEGSLSDEQGMPQNRLLILILSVIFIKGNCASEEVIWEVLN
  AIGPWSALAGFADVLSRLALWESEGPEAFCEESGLRSAEGSVLDLANPQGLAGHRQEDGR
  RGLTEASPQQKKGGEDEDMPAAGMPPLPQSPPEIPPQGPPKISPQGPPQSPPQSPLDSCS
  SPLLWTRLDEESSSEEEDTATWHALPESESLPRYALDEKVAELVQFLLLKYQTKEPVTKA
  EMLTTVIKKYKDYFPMIFGKAHEFIELIFGIALTDMDPDNHSYFFEDTLDLTYEGSLIDD
  QGMPKNCLLILILSMIFIKGSCVPEEVIWEVLSAIGPIQRPAREVLEFLSKLSSIIPSAF
  PSWYMDALKDMEDRAQAIIDTTDDATAMASASPSVMSTNFCPE
• Tissue Specificity: Expressed in testis. Not expressed in other normal tissues, but is expressed in tumors of different histological origins.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Infantile malignant osteopetrosis	DIS8C3LZ	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Metabolic bone disease	DISO7RI8	Strong	Genetic Variation	[4]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[5]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[6]
Obesity	DIS47Y1K	Strong	Biomarker	[3]
Autosomal recessive osteopetrosis 3	DISWBB4P	moderate	Genetic Variation	[4]
Diabetic retinopathy	DISHGUJM	moderate	Biomarker	[7]
Retinopathy	DISB4B0F	moderate	Biomarker	[7]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[8]
Leiomyoma	DISLDDFN	Limited	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]
Uterine fibroids	DISBZRMJ	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Melanoma-associated antigen C3 (MAGEC3).	[10]

References

• [1] The determination of osteopetrotic phenotypes by selective inactivation of red cell carbonic anhydrase isoenzymes.Clin Chim Acta. 1985 Nov 15;152(3):347-54. doi: 10.1016/0009-8981(85)90110-x.
• [2] Novel sulfamate derivatives of menthol: Synthesis, characterization, and cholinesterases and carbonic anhydrase enzymes inhibition properties.Arch Pharm (Weinheim). 2018 Nov;351(11):e1800209. doi: 10.1002/ardp.201800209. Epub 2018 Sep 26.
• [3] Hydroxycarboxylic Acid Receptor Ligands Modulate Proinflammatory Cytokine Expression in Human Macrophages and Adipocytes without Affecting Adipose Differentiation.Biol Pharm Bull. 2018;41(10):1574-1580. doi: 10.1248/bpb.b18-00301.
• [4] Small-molecule suppression of misfolding of mutated human carbonic anhydrase II linked to marble brain disease.Biochemistry. 2009 Jun 16;48(23):5358-64. doi: 10.1021/bi900128e.
• [5] Increased infiltration of M2-macrophages, T-cells and PD-L1 expression in high grade leiomyosarcomas supports immunotherapeutic strategies.Oncoimmunology. 2017 Oct 26;7(2):e1386828. doi: 10.1080/2162402X.2017.1386828. eCollection 2018.
• [6] Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population.Gene. 2018 Nov 30;677:324-331. doi: 10.1016/j.gene.2018.08.041. Epub 2018 Aug 18.
• [7] Constitutive expression of HCA(2) in human retina and primary human retinal pigment epithelial cells.Curr Eye Res. 2014 May;39(5):487-92. doi: 10.3109/02713683.2013.848900. Epub 2013 Nov 11.
• [8] Continued exploration and tail approach synthesis of benzenesulfonamides containing triazole and dual triazole moieties as carbonic anhydrase I, II, IV and IX inhibitors.Eur J Med Chem. 2019 Dec 1;183:111698. doi: 10.1016/j.ejmech.2019.111698. Epub 2019 Sep 12.
• [9] Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors.J Enzyme Inhib Med Chem. 2017 Dec;32(1):1274-1281. doi: 10.1080/14756366.2017.1380638.
• [10] 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.