Details of Drug Off-Target (DOT)

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

• DOT Name: Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B)
• Gene Name: TIMM17B
• UniProt ID: TI17B_HUMAN
• Pfam ID: PF02466
• Sequence:
  MEEYAREPCPWRIVDDCGGAFTMGVIGGGVFQAIKGFRNAPVGIRHRLRGSANAVRIRAP
  QIGGSFAVWGGLFSTIDCGLVRLRGKEDPWNSITSGALTGAVLAARSGPLAMVGSAMMGG
  ILLALIEGVGILLTRYTAQQFRNAPPFLEDPSQLPPKDGTPAPGYPSYQQYH
• Function: Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.
• Tissue Specificity: Expression is abundant in heart and skeletal muscle, intermediate in brain, and weak in pancreas, placenta, kidney and liver.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

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 Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[4]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[5]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[3]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[3]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitochondrial import inner membrane translocase subunit Tim17-B (TIMM17B).	[6]

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] 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.
• [3] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [4] 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.
• [5] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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.