Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT87AT1X)

• DOT Name: Protein LBH (LBH)
• Synonyms: hLBH; Limb bud and heart development protein homolog
• Gene Name: LBH
• Related Disease:
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Alzheimer disease
  Cardiac disease
  Childhood acute lymphoblastic leukemia
  Chondrosarcoma
  Lupus
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Synovial sarcoma
  Systemic lupus erythematosus
  Uveal Melanoma
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Primary cutaneous T-cell lymphoma
  Varicose veins
  Plasma cell myeloma
• UniProt ID: LBH_HUMAN
• Pfam ID: PF15317
• Sequence:
  MSIYFPIHCPDYLRSAKMTEVMMNTQPMEEIGLSPRKDGLSYQIFPDPSDFDRCCKLKDR
  LPSIVVEPTEGEVESGELRWPPEEFLVQEDEQDNCEETAKENKEQ
• Function: Transcriptional activator which may act in mitogen-activated protein kinase signaling pathway.
• Tissue Specificity: Highly expressed in heart, and expressed at low levels in placenta, lung, skeletal muscle, kidney and liver.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Cardiac disease	DISVO1I5	Strong	Biomarker	[4]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[1]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[5]
Lupus	DISOKJWA	Strong	Genetic Variation	[6]
Prostate cancer	DISF190Y	Strong	Altered Expression	[7]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[7]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[6]
Synovial sarcoma	DISEZJS7	Strong	Biomarker	[5]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[8]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[9]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	moderate	Biomarker	[10]
Primary cutaneous T-cell lymphoma	DIS35WVW	moderate	Biomarker	[10]
Varicose veins	DISIMBN2	moderate	Genetic Variation	[11]
Plasma cell myeloma	DIS0DFZ0	Disputed	Biomarker	[10]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Protein LBH (LBH) affects the response to substance of Mitoxantrone.	[37]

25 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 Protein LBH (LBH).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein LBH (LBH).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein LBH (LBH).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein LBH (LBH).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein LBH (LBH).	[16]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein LBH (LBH).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein LBH (LBH).	[18]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein LBH (LBH).	[19]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein LBH (LBH).	[20]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein LBH (LBH).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein LBH (LBH).	[22]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Protein LBH (LBH).	[23]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein LBH (LBH).	[24]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein LBH (LBH).	[25]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Protein LBH (LBH).	[26]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Protein LBH (LBH).	[27]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Protein LBH (LBH).	[28]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Protein LBH (LBH).	[29]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein LBH (LBH).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein LBH (LBH).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein LBH (LBH).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein LBH (LBH).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein LBH (LBH).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein LBH (LBH).	[35]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Protein LBH (LBH).	[36]

References

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• [2] Panobinostat for the treatment of acute myelogenous leukemia.Expert Opin Investig Drugs. 2016 Sep;25(9):1117-31. doi: 10.1080/13543784.2016.1216971. Epub 2016 Aug 8.
• [3] Integrated analysis of human genetic association study and mouse transcriptome suggests LBH and SHF genes as novel susceptible genes for amyloid- accumulation in Alzheimer's disease.Hum Genet. 2018 Jul;137(6-7):521-533. doi: 10.1007/s00439-018-1906-z. Epub 2018 Jul 13.
• [4] Congenital heart disease reminiscent of partial trisomy 2p syndrome in mice transgenic for the transcription factor Lbh.Development. 2005 Jul;132(14):3305-16. doi: 10.1242/dev.01887. Epub 2005 Jun 15.
• [5] Histone deacetylase inhibitors vorinostat and panobinostat induce G1 cell cycle arrest and apoptosis in multidrug resistant sarcoma cell lines.Oncotarget. 2017 Aug 24;8(44):77254-77267. doi: 10.18632/oncotarget.20460. eCollection 2017 Sep 29.
• [6] LBH Gene Transcription Regulation by the Interplay of an Enhancer Risk Allele and DNA Methylation in Rheumatoid Arthritis.Arthritis Rheumatol. 2016 Nov;68(11):2637-2645. doi: 10.1002/art.39746.
• [7] Limb-bud and Heart Overexpression Inhibits the Proliferation and Migration of PC3M Cells.J Cancer. 2018 Jan 1;9(2):424-432. doi: 10.7150/jca.21375. eCollection 2018.
• [8] Downregulated expression of LBH mRNA in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.J Dermatol. 2016 Jan;43(1):99-102. doi: 10.1111/1346-8138.13006. Epub 2015 Jun 30.
• [9] The Role of Histone Deacetylase Inhibitors in Uveal Melanoma: Current Evidence.Anticancer Res. 2018 Jul;38(7):3817-3824. doi: 10.21873/anticanres.12665.
• [10] Zinc-dependent Deacetylase (HDAC) Inhibitors with Different Zinc Binding Groups.Curr Top Med Chem. 2019;19(3):223-241. doi: 10.2174/1568026619666190122144949.
• [11] Clinical and Genetic Determinants of Varicose Veins.Circulation. 2018 Dec 18;138(25):2869-2880. doi: 10.1161/CIRCULATIONAHA.118.035584.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [18] 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.
• [19] 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.
• [20] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [21] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [22] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] 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.
• [25] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [26] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [27] 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.
• [28] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [29] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [30] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [31] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
• [32] 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.
• [33] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [34] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [35] 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.
• [36] 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.
• [37] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.