Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZJQG1D)

• DOT Name: MOB kinase activator 3B (MOB3B)
• Synonyms: Mob1 homolog 2b; Mps one binder kinase activator-like 2B; MOB kinase activator-like 2B
• Gene Name: MOB3B
• Related Disease:
  Advanced cancer
  Amyotrophic lateral sclerosis
  Prostate carcinoma
• UniProt ID: MOB3B_HUMAN
• Pfam ID: PF03637
• Sequence:
  MSIALKQVFNKDKTFRPKRKFEPGTQRFELHKRAQASLNSGVDLKAAVQLPSGEDQNDWV
  AVHVVDFFNRINLIYGTICEFCTERTCPVMSGGPKYEYRWQDDLKYKKPTALPAPQYMNL
  LMDWIEVQINNEEIFPTCVGVPFPKNFLQICKKILCRLFRVFVHVYIHHFDRVIVMGAEA
  HVNTCYKHFYYFVTEMNLIDRKELEPLKEMTSRMCH
• Function: Modulates LATS1 expression in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[2]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of MOB kinase activator 3B (MOB3B).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of MOB kinase activator 3B (MOB3B).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of MOB kinase activator 3B (MOB3B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of MOB kinase activator 3B (MOB3B).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of MOB kinase activator 3B (MOB3B).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of MOB kinase activator 3B (MOB3B).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of MOB kinase activator 3B (MOB3B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of MOB kinase activator 3B (MOB3B).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of MOB kinase activator 3B (MOB3B).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of MOB kinase activator 3B (MOB3B).	[13]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of MOB kinase activator 3B (MOB3B).	[14]

References

• [1] DNA methylation signatures for prediction of biochemical recurrence after radical prostatectomy of clinically localized prostate cancer.J Clin Oncol. 2013 Sep 10;31(26):3250-8. doi: 10.1200/JCO.2012.47.1847. Epub 2013 Aug 5.
• [2] Second-generation Irish genome-wide association study for amyotrophic lateral sclerosis.Neurobiol Aging. 2015 Feb;36(2):1221.e7-13. doi: 10.1016/j.neurobiolaging.2014.08.030. Epub 2014 Sep 6.
• [3] A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of urinary symptoms after radiotherapy for prostate cancer.J Urol. 2013 Jul;190(1):102-8. doi: 10.1016/j.juro.2013.01.096. Epub 2013 Feb 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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [9] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.