Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRJU667)

• DOT Name: Transmembrane protein 60 (TMEM60)
• Gene Name: TMEM60
• Related Disease:
  Arthritis
  Autoimmune disease
  Rheumatoid arthritis
  Chronic kidney disease
  Osteoarthritis
• UniProt ID: TMM60_HUMAN
• Pfam ID: PF10269
• Sequence:
  MRMSLAQRVLLTWLFTLLFLIMLVLKLDEKAPWNWFLIFIPVWIFDTILLVLLIVKMAGR
  CKSGFDPRHGSHNIKKKAWYLIAMLLKLAFCLALCAKLEQFTTMNLSYVFIPLWALLAGA
  LTELGYNVFFVRD

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Strong	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[1]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[1]
Chronic kidney disease	DISW82R7	moderate	Genetic Variation	[2]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[3]

1 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 Transmembrane protein 60 (TMEM60).	[4]

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 Transmembrane protein 60 (TMEM60).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 60 (TMEM60).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 60 (TMEM60).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transmembrane protein 60 (TMEM60).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 60 (TMEM60).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transmembrane protein 60 (TMEM60).	[10]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Transmembrane protein 60 (TMEM60).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 60 (TMEM60).	[12]

References

• [1] Dihydroartemisinin derivative DC32 attenuates collagen-induced arthritis in mice by restoring the Treg/Th17 balance and inhibiting synovitis through down-regulation of IL-6.Int Immunopharmacol. 2018 Dec;65:233-243. doi: 10.1016/j.intimp.2018.10.015. Epub 2018 Oct 15.
• [2] New loci associated with kidney function and chronic kidney disease.Nat Genet. 2010 May;42(5):376-84. doi: 10.1038/ng.568. Epub 2010 Apr 11.
• [3] Dihydroartemisinin derivative DC32 inhibits inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-B pathway.Int Immunopharmacol. 2019 Sep;74:105701. doi: 10.1016/j.intimp.2019.105701. Epub 2019 Jun 19.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] 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.
• [11] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.