Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT312DUH)

• DOT Name: Myelin-associated neurite-outgrowth inhibitor (FAM168B)
• Synonyms: Mani; p20
• Gene Name: FAM168B
• Related Disease:
  Becker muscular dystrophy
  Duchenne muscular dystrophy
  Fatty liver disease
  Glioma
  Neoplasm
• UniProt ID: F168B_HUMAN
• Pfam ID: PF14944
• Sequence:
  MNPVYSPGSSGVPYANAKGIGYPAGFPMGYAAAAPAYSPNMYPGANPTFQTGYTPGTPYK
  VSCSPTSGAVPPYSSSPNPYQTAVYPVRSAYPQQSPYAQQGTYYTQPLYAAPPHVIHHTT
  VVQPNGMPATVYPAPIPPPRGNGVTMGMVAGTTMAMSAGTLLTAHSPTPVAPHPVTVPTY
  RAPGTPTYSYVPPQW
• Function: Inhibitor of neuronal axonal outgrowth. Acts as a negative regulator of CDC42 and STAT3 and a positive regulator of STMN2. Positive regulator of CDC27.
• Tissue Specificity: Expressed in the brain, within neuronal axonal fibers and associated with myelin sheets (at protein level). Expression tends to be lower in the brain of Alzheimer disease patients compared to healthy individuals (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Becker muscular dystrophy	DIS5IYHL	Definitive	Biomarker	[1]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[2]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]

3 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 Myelin-associated neurite-outgrowth inhibitor (FAM168B).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Myelin-associated neurite-outgrowth inhibitor (FAM168B).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myelin-associated neurite-outgrowth inhibitor (FAM168B).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Myelin-associated neurite-outgrowth inhibitor (FAM168B).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Myelin-associated neurite-outgrowth inhibitor (FAM168B).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Myelin-associated neurite-outgrowth inhibitor (FAM168B).	[10]

References

• [1] A deletion hot spot in the Duchenne muscular dystrophy gene.Genomics. 1988 Feb;2(2):101-8. doi: 10.1016/0888-7543(88)90090-0.
• [2] Identification of Duchenne muscular dystrophy genomic probe P20 constant Taql fragment corresponding to the EcoRV and Mspl polymorphisms.Prenat Diagn. 1991 Jan;11(1):63-7. doi: 10.1002/pd.1970110112.
• [3] Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice.Cell Mol Immunol. 2019 Nov;16(11):878-886. doi: 10.1038/s41423-018-0032-0. Epub 2018 May 7.
• [4] Paxilline enhances TRAIL-mediated apoptosis of glioma cells via modulation of c-FLIP, survivin and DR5.Exp Mol Med. 2011 Jan 31;43(1):24-34. doi: 10.3858/emm.2011.43.1.003.
• [5] Inhibition of melanoma metastasis by dual-peptide PLGA NPS.Biopolymers. 2017 Sep;108(5). doi: 10.1002/bip.23029.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] 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.
• [9] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [10] 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.