Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT85SX7C)

• DOT Name: SPRY domain-containing protein 4 (SPRYD4)
• Gene Name: SPRYD4
• Related Disease: Hepatocellular carcinoma
• UniProt ID: SPRY4_HUMAN
• Pfam ID: PF00622
• Sequence:
  MALLFARSLRLCRWGAKRLGVASTEAQRGVSFKLEEKTAHSSLALFRDDTGVKYGLVGLE
  PTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSRDSCIGVDDR
  SWVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDF
  RGPVVPAFALWDGELLTHSGLEVPEGL

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]

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 SPRY domain-containing protein 4 (SPRYD4).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SPRY domain-containing protein 4 (SPRYD4).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SPRY domain-containing protein 4 (SPRYD4).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SPRY domain-containing protein 4 (SPRYD4).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of SPRY domain-containing protein 4 (SPRYD4).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of SPRY domain-containing protein 4 (SPRYD4).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of SPRY domain-containing protein 4 (SPRYD4).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of SPRY domain-containing protein 4 (SPRYD4).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of SPRY domain-containing protein 4 (SPRYD4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SPRY domain-containing protein 4 (SPRYD4).	[11]

References

• [1] Novel tumor suppressor SPRYD4 inhibits tumor progression in hepatocellular carcinoma by inducing apoptotic cell death.Cell Oncol (Dordr). 2019 Feb;42(1):55-66. doi: 10.1007/s13402-018-0407-3. Epub 2018 Sep 20.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.