Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKII63K)

• DOT Name: Fidgetin-like protein 1 (FIGNL1)
• Synonyms: EC 3.6.4.-
• Gene Name: FIGNL1
• Related Disease:
  Aromatic L-amino acid decarboxylase deficiency
  Kidney cancer
  Kidney neoplasm
  Small-cell lung cancer
• UniProt ID: FIGL1_HUMAN
• PDB ID: 3D8B
• EC Number: 3.6.4.-
• Pfam ID: PF00004 ; PF17862 ; PF09336
• Sequence:
  MQTSSSRSVHLSEWQKNYFAITSGICTGPKADAYRAQILRIQYAWANSEISQVCATKLFK
  KYAEKYSAIIDSDNVESGLNNYAENILTLAGSQQTDSDKWQSGLSINNVFKMSSVQKMMQ
  AGKKFKDSLLEPALASVVIHKEATVFDLPKFSVCGSSQESDSLPNSAHDRDRTQDFPESN
  RLKLLQNAQPPMVTNTARTCPTFSAPVGESATAKFHVTPLFGNVKKENHSSAKENIGLNV
  FLSNQSCFPAACENPQRKSFYGSGTIDALSNPILNKACSKTEDNGPKEDSSLPTFKTAKE
  QLWVDQQKKYHQPQRASGSSYGGVKKSLGASRSRGILGKFVPPIPKQDGGEQNGGMQCKP
  YGAGPTEPAHPVDERLKNLEPKMIELIMNEIMDHGPPVNWEDIAGVEFAKATIKEIVVWP
  MLRPDIFTGLRGPPKGILLFGPPGTGKTLIGKCIASQSGATFFSISASSLTSKWVGEGEK
  MVRALFAVARCQQPAVIFIDEIDSLLSQRGDGEHESSRRIKTEFLVQLDGATTSSEDRIL
  VVGATNRPQEIDEAARRRLVKRLYIPLPEASARKQIVINLMSKEQCCLSEEEIEQIVQQS
  DAFSGADMTQLCREASLGPIRSLQTADIATITPDQVRPIAYIDFENAFRTVRPSVSPKDL
  ELYENWNKTFGCGK
• Function: Involved in DNA double-strand break (DBS) repair via homologous recombination (HR). Recruited at DSB sites independently of BRCA2, RAD51 and RAD51 paralogs in a H2AX-dependent manner. May regulate osteoblast proliferation and differentiation. May play a role in the control of male meiosis dynamic.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aromatic L-amino acid decarboxylase deficiency	DIS3C407	Strong	Genetic Variation	[1]
Kidney cancer	DISBIPKM	Strong	Biomarker	[2]
Kidney neoplasm	DISBNZTN	Strong	Biomarker	[2]
Small-cell lung cancer	DISK3LZD	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Fidgetin-like protein 1 (FIGNL1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Fidgetin-like protein 1 (FIGNL1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Fidgetin-like protein 1 (FIGNL1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fidgetin-like protein 1 (FIGNL1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fidgetin-like protein 1 (FIGNL1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Fidgetin-like protein 1 (FIGNL1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Fidgetin-like protein 1 (FIGNL1).	[14]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[15]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Fidgetin-like protein 1 (FIGNL1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Fidgetin-like protein 1 (FIGNL1).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Fidgetin-like protein 1 (FIGNL1).	[10]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fidgetin-like protein 1 (FIGNL1).	[17]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Fidgetin-like protein 1 (FIGNL1).	[18]

References

• [1] Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology. 2010 Jul 6;75(1):64-71. doi: 10.1212/WNL.0b013e3181e620ae. Epub 2010 May 26.
• [2] Investigation of the early-response genes in chemical-induced renal carcinogenicity for the prediction of chemical carcinogenicity in rats.J Toxicol Sci. 2017;42(2):175-181. doi: 10.2131/jts.42.175.
• [3] FIGNL1 is overexpressed in small cell lung cancer patients and enhances NCI-H446 cell resistance to cisplatin and etoposide.Oncol Rep. 2017 Apr;37(4):1935-1942. doi: 10.3892/or.2017.5483. Epub 2017 Mar 1.
• [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] 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.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [11] 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.
• [12] 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.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] 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.
• [16] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [17] 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.
• [18] 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.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.