Details of Drug Off-Target (DOT)

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

• DOT Name: Testis development-related protein (TDRP)
• Synonyms: Protein INM01
• Gene Name: TDRP
• UniProt ID: TDRP_HUMAN
• Pfam ID: PF15683
• Sequence:
  MWKLGRGRVLLDEPPEEEDGLRGGPPPAAAAAAQAQVQGASFRGWKEVTSLFNKDDEQHL
  LERCKSPKSKGTNLRLKEELKAEKKSGFWDNLVLKQNIQSKKPDEIEGWEPPKLALEDIS
  ADPEDTVGGHPSWSGWEDDAKGSTKYTSLASSANSSRWSLRAAGRLVSIRRQSKGHLTDS
  PEEAE
• Function: Contributes to normal sperm motility, but not essential for male fertility.
• Tissue Specificity: Expressed in spermatogenic cells, especially in spermatocytes (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Testis development-related protein (TDRP) affects the response to substance of Temozolomide.	[9]
DTI-015	DMXZRW0	Approved	Testis development-related protein (TDRP) affects the response to substance of DTI-015.	[9]

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 Testis development-related protein (TDRP).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Testis development-related protein (TDRP).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Testis development-related protein (TDRP).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Testis development-related protein (TDRP).	[2]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Testis development-related protein (TDRP).	[3]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Testis development-related protein (TDRP).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Testis development-related protein (TDRP).	[2]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Testis development-related protein (TDRP).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Testis development-related protein (TDRP).	[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] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [3] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [4] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [5] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.