Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTALLHT1)

• DOT Name: FIGNL1-interacting regulator of recombination and mitosis (FIRRM)
• Synonyms: FIDGETIN-like-1 interacting protein; FLIP; POLO1-associating protein
• Gene Name: FIRRM
• UniProt ID: FIRRM_HUMAN
• Pfam ID: PF14868
• Sequence:
  MFLPHMNHLTLEQTFFSQVLPKTVKLFDDMMYELTSQARGLSSQNLEIQTTLRNILQTMV
  QLLGALTGCVQHICATQESIILENIQSLPSSVLHIIKSTFVHCKNSESVYSGCLHLVSDL
  LQALFKEAYSLQKQLMELLDMVCMDPLVDDNDDILNMVIVIHSLLDICSVISSMDHAFHA
  NTWKFIIKQSLKHQSIIKSQLKHKDIITSLCEDILFSFHSCLQLAEQMTQSDAQDNADYR
  LFQKTLKLCRFFANSLLHYAKEFLPFLSDSCCTLHQLYLQIHSKFPPSLYATRISKAHQE
  EIAGAFLVTLDPLISQLLTFQPFMQVVLDSKLDLPCELQFPQCLLLVVVMDKLPSQPKEV
  QTLWCTDSQVSETTTRISLLKAVFYSFEQCSGELSLPVHLQGLKSKGKAEVAVTLYQHVC
  VHLCTFITSFHPSLFAELDAALLNAVLSANMITSLLAMDAWCFLARYGTAELCAHHVTIV
  AHLIKSCPGECYQLINLSILLKRLFFFMAPPHQLEFIQKFSPKEAENLPLWQHISFQALP
  PELREQTVHEVTTVGTAECRKWLSRSRTLGELESLNTVLSALLAVCNSAGEALDTGKQTA
  IIEVVSQLWAFLNIKQVADQPYVQQTFSLLLPLLGFFIQTLDPKLILQAVTLQTSLLKLE
  LPDYVRLAMLDFVSSLGKLFIPEAIQDRILPNLSCMFALLLADRSWLLEQHTLEAFTQFA
  EGTNHEEIVPQCLSSEETKNKVVSFLEKTGFVDETEAAKVERVKQEKGIFWEPFANVTVE
  EAKRSSLQPYAKRARQEFPWEEEYRSALHTIAGALEATESLLQKGPAPAWLSMEMEALQE
  RMDKLKRYIHTLG
• Function: Regulates PLK1 kinase activity at kinetochores and promotes faithful chromosome segregation in prometaphase by bridging kinase and phosphatase activities. Phosphorylation of FIRRM by PLK1 negatively regulates its interaction with the phosphatase, PPP1CC, thus creating a negative feedback loop for maintaining proper PLK1 kinase activity during mitosis. In complex with FIGL1 may regulate homologous recombination.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[6]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[7]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[9]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of FIGNL1-interacting regulator of recombination and mitosis (FIRRM).	[12]

References

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• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [10] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [12] 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.
• [13] 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.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
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