Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6CRZEU)

• DOT Name: Jupiter microtubule associated homolog 1 (JPT1)
• Synonyms: Androgen-regulated protein 2; Hematological and neurological expressed 1 protein
• Gene Name: JPT1
• Related Disease:
  Advanced cancer
  Epithelial ovarian cancer
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Leukopenia
  Liver cirrhosis
  Prostate cancer
  Prostate carcinoma
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: JUPI1_HUMAN
• Pfam ID: PF17054
• Sequence:
  MTTTTTFKGVDPNSRNSSRVLRPPGGGSNFSLGFDEPTEQPVRKNKMASNIFGTPEENQA
  SWAKSAGAKSSGGREDLESSGLQRRNSSEASSGDFLDLKGEGDIHENVDTDLPGSLGQSE
  EKPVPAAPVPSPVAPAPVPSRRNPPGGKSSLVLG
• Function: Modulates negatively AKT-mediated GSK3B signaling. Induces CTNNB1 'Ser-33' phosphorylation and degradation through the suppression of the inhibitory 'Ser-9' phosphorylation of GSK3B, which represses the function of the APC:CTNNB1:GSK3B complex and the interaction with CDH1/E-cadherin in adherent junctions. Plays a role in the regulation of cell cycle and cell adhesion. Has an inhibitory role on AR-signaling pathway through the induction of receptor proteasomal degradation.
• Tissue Specificity: Expressed in testis, skeletal muscle, thymus, prostate, colon, peripheral blood cells, brain and placenta.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[4]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[7]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[8]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[9]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[9]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[10]
Neoplasm	DISZKGEW	Limited	Biomarker	[11]

18 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 Jupiter microtubule associated homolog 1 (JPT1).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[21]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[22]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Jupiter microtubule associated homolog 1 (JPT1).	[27]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Jupiter microtubule associated homolog 1 (JPT1).	[28]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Jupiter microtubule associated homolog 1 (JPT1).	[29]

References

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• [3] HN1 contributes to migration, invasion, and tumorigenesis of breast cancer by enhancing MYC activity.Mol Cancer. 2017 May 11;16(1):90. doi: 10.1186/s12943-017-0656-1.
• [4] Jupiter microtubule-associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers.Cancer Med. 2020 Feb;9(3):1092-1103. doi: 10.1002/cam4.2729. Epub 2019 Dec 6.
• [5] All-oral combination of ledipasvir, vedroprevir, tegobuvir, and ribavirin in treatment-nave patients with genotype 1 HCV infection.Hepatology. 2014 Jul;60(1):56-64. doi: 10.1002/hep.27053. Epub 2014 May 28.
• [6] Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down-regulation of c-Met.Kaohsiung J Med Sci. 2020 Mar;36(3):196-205. doi: 10.1002/kjm2.12156. Epub 2019 Nov 20.
• [7] Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer.Breast Cancer Res Treat. 2015 Jan;149(1):151-61. doi: 10.1007/s10549-014-3248-4. Epub 2014 Dec 24.
• [8] Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study.Transpl Int. 2017 Feb;30(2):196-208. doi: 10.1111/tri.12896. Epub 2017 Jan 20.
• [9] The role of hypofractionated radiotherapy for the definitive treatment of localized prostate cancer: early results of a randomized trial.J Cancer. 2019 Oct 16;10(25):6217-6224. doi: 10.7150/jca.35510. eCollection 2019.
• [10] Phase II study of Dovitinib in recurrent glioblastoma.J Neurooncol. 2019 Sep;144(2):359-368. doi: 10.1007/s11060-019-03236-6. Epub 2019 Jul 11.
• [11] Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis.Clin Cancer Res. 2004 May 15;10(10):3291-300. doi: 10.1158/1078-0432.CCR-03-0409.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [16] 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.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [19] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [20] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [25] 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.
• [26] 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.
• [27] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [29] The marine toxin okadaic acid induces alterations in the expression level of cancer-related genes in human neuronal cells. Ecotoxicol Environ Saf. 2013 Jun;92:303-11. doi: 10.1016/j.ecoenv.2013.03.009. Epub 2013 Apr 3.