Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9IQ9NV)

• DOT Name: Serine protease FAM111B (FAM111B)
• Synonyms: EC 3.4.21.-; Cancer-associated nucleoprotein
• Gene Name: FAM111B
• Related Disease:
  Hepatocellular carcinoma
  Clear cell renal carcinoma
  Duchenne muscular dystrophy
  Erythrokeratodermia variabilis
  Hereditary sclerosing poikiloderma with tendon and pulmonary involvement
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Myopathy
  Neoplasm
  Papillary renal cell carcinoma
  Pulmonary fibrosis
  Renal cell carcinoma
  Rothmund-Thomson syndrome
• UniProt ID: F111B_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF13365
• Sequence:
  MNSMKTEENKSFSAMEDDQRTRPEVSKDTVMKQTHADTPVDHCLSGIRKCSSTFKLKSEV
  NKHETALEMQNPNLNNKECCFTFTLNGNSRKLDRSVFTAYGKPSESIYSALSANDYFSER
  IKNQFNKNIIVYEEKTIDGHINLGMPLKCLPSDSHFKITFGQRKSSKEDGHILRQCENPN
  MECILFHVVAIGRTRKKIVKINELHEKGSKLCIYALKGETIEGALCKDGRFRSDIGEFEW
  KLKEGHKKIYGKQSMVDEVSGKVLEMDISKKKALQQKDIHKKIKQNESATDEINHQSLIQ
  SKKKVHKPKKDGETKDVEHSREQILPPQDLSHYIKDKTRQTIPRIRNYYFCSLPRKYRQI
  NSQVRRRPHLGRRYAINLDVQKEAINLLKNYQTLNEAIMHQYPNFKEEAQWVRKYFREEQ
  KRMNLSPAKQFNIYKKDFGKMTANSVSVATCEQLTYYSKSVGFMQWDNNGNTGNATCFVF
  NGGYIFTCRHVVHLMVGKNTHPSLWPDIISKCAKVTFTYTEFCPTPDNWFSIEPWLKVSN
  ENLDYAILKLKENGNAFPPGLWRQISPQPSTGLIYLIGHPEGQIKKIDGCTVIPLNERLK
  KYPNDCQDGLVDLYDTTSNVYCMFTQRSFLSEVWNTHTLSYDTCFSDGSSGSPVFNASGK
  LVALHTFGLFYQRGFNVHALIEFGYSMDSILCDIKKTNESLYKSLNDEKLETYDEEKGKQ
  ESSLQDHQIEPMEC
• Function: Serine protease.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[3]
Erythrokeratodermia variabilis	DIS4BMUQ	Strong	Biomarker	[4]
Hereditary sclerosing poikiloderma with tendon and pulmonary involvement	DISSJUS7	Strong	Autosomal dominant	[4]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[5]
Myopathy	DISOWG27	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[2]
Pulmonary fibrosis	DISQKVLA	Strong	Genetic Variation	[6]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[2]
Rothmund-Thomson syndrome	DISGVBCV	Strong	Biomarker	[4]

22 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 Serine protease FAM111B (FAM111B).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine protease FAM111B (FAM111B).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine protease FAM111B (FAM111B).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serine protease FAM111B (FAM111B).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine protease FAM111B (FAM111B).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine protease FAM111B (FAM111B).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Serine protease FAM111B (FAM111B).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Serine protease FAM111B (FAM111B).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Serine protease FAM111B (FAM111B).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Serine protease FAM111B (FAM111B).	[15]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Serine protease FAM111B (FAM111B).	[1]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Serine protease FAM111B (FAM111B).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Serine protease FAM111B (FAM111B).	[18]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Serine protease FAM111B (FAM111B).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine protease FAM111B (FAM111B).	[20]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Serine protease FAM111B (FAM111B).	[21]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Serine protease FAM111B (FAM111B).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine protease FAM111B (FAM111B).	[23]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Serine protease FAM111B (FAM111B).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine protease FAM111B (FAM111B).	[26]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Serine protease FAM111B (FAM111B).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine protease FAM111B (FAM111B).	[28]

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 decreases the sumoylation of Serine protease FAM111B (FAM111B).	[25]

References

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• [2] Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma.Nat Genet. 2011 Dec 4;44(1):17-9. doi: 10.1038/ng.1014.
• [3] Importance of monitoring calcium & calcium related properties in carrier detection for Duchenne muscular dystrophy.Indian J Med Res. 1994 Jun;99:283-8.
• [4] Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis. Am J Hum Genet. 2013 Dec 5;93(6):1100-7. doi: 10.1016/j.ajhg.2013.10.013. Epub 2013 Nov 21.
• [5] FAM111B, a direct target of p53, promotes the malignant process of lung adenocarcinoma.Onco Targets Ther. 2019 Apr 17;12:2829-2842. doi: 10.2147/OTT.S190934. eCollection 2019.
• [6] Family of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis caused by a novel FAM111B mutation.J Dermatol. 2019 Nov;46(11):1014-1018. doi: 10.1111/1346-8138.15045. Epub 2019 Aug 7.
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• [10] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
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• [12] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [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] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
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• [17] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [18] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [19] 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.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [22] 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.
• [23] 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.
• [24] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [25] 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.
• [26] 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.
• [27] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [28] 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.