Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6M13ZV)

• DOT Name: Glutamate-rich WD repeat-containing protein 1 (GRWD1)
• Gene Name: GRWD1
• Related Disease:
  Lung adenocarcinoma
  Neoplasm
  Advanced cancer
  Cutaneous melanoma
• UniProt ID: GRWD1_HUMAN
• Pfam ID: PF12265 ; PF00400
• Sequence:
  MAARKGRRRTCETGEPMEAESGDTSSEGPAQVYLPGRGPPLREGEELVMDEEAYVLYHRA
  QTGAPCLSFDIVRDHLGDNRTELPLTLYLCAGTQAESAQSNRLMMLRMHNLHGTKPPPSE
  GSDEEEEEEDEEDEEERKPQLELAMVPHYGGINRVRVSWLGEEPVAGVWSEKGQVEVFAL
  RRLLQVVEEPQALAAFLRDEQAQMKPIFSFAGHMGEGFALDWSPRVTGRLLTGDCQKNIH
  LWTPTDGGSWHVDQRPFVGHTRSVEDLQWSPTENTVFASCSADASIRIWDIRAAPSKACM
  LTTATAHDGDVNVISWSRREPFLLSGGDDGALKIWDLRQFKSGSPVATFKQHVAPVTSVE
  WHPQDSGVFAASGADHQITQWDLAVERDPEAGDVEADPGLADLPQQLLFVHQGETELKEL
  HWHPQCPGLLVSTALSGFTIFRTISV
• Function: Histone binding-protein that regulates chromatin dynamics and minichromosome maintenance (MCM) loading at replication origins, possibly by promoting chromatin openness.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]
Cutaneous melanoma	DIS3MMH9	Limited	Altered Expression	[3]

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 Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[4]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[9]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glutamate-rich WD repeat-containing protein 1 (GRWD1).	[15]

References

• [1] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [2] GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system.J Cell Sci. 2018 Aug 3;131(15):jcs213009. doi: 10.1242/jcs.213009.
• [3] GRWD1 directly interacts with p53 and negatively regulates p53 transcriptional activity.J Biochem. 2020 Jan 1;167(1):15-24. doi: 10.1093/jb/mvz075.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.