Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2HPHEI)

• DOT Name: Golgi-associated kinase 1B (GASK1B)
• Synonyms: Expressed in nerve and epithelium during development; Protein FAM198B
• Gene Name: GASK1B
• Related Disease:
  Advanced cancer
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
• UniProt ID: GAK1B_HUMAN
• Pfam ID: PF15051
• Sequence:
  MTCPDKPGQLINWFICSLCVPRVRKLWSSRRPRTRRNLLLGTACAIYLGFLVSQVGRASL
  QHGQAAEKGPHRSRDTAEPSFPEIPLDGTLAPPESQGNGSTLQPNVVYITLRSKRSKPAN
  IRGTVKPKRRKKHAVASAAPGQEALVGPSLQPQEAAREADAVAPGYAQGANLVKIGERPW
  RLVRGPGVRAGGPDFLQPSSRESNIRIYSESAPSWLSKDDIRRMRLLADSAVAGLRPVSS
  RSGARLLVLEGGAPGAVLRCGPSPCGLLKQPLDMSEVFAFHLDRILGLNRTLPSVSRKAE
  FIQDGRPCPIILWDASLSSASNDTHSSVKLTWGTYQQLLKQKCWQNGRVPKPESGCTEIH
  HHEWSKMALFDFLLQIYNRLDTNCCGFRPRKEDACVQNGLRPKCDDQGSAALAHIIQRKH
  DPRHLVFIDNKGFFDRSEDNLNFKLLEGIKEFPASAVSVLKSQHLRQKLLQSLFLDKVYW
  ESQGGRQGIEKLIDVIEHRAKILITYINAHGVKVLPMNE

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Limited	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[1]
Lung cancer	DISCM4YA	Limited	Altered Expression	[1]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[1]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Golgi-associated kinase 1B (GASK1B).	[2]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Golgi-associated kinase 1B (GASK1B).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Golgi-associated kinase 1B (GASK1B).	[28]

27 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 Golgi-associated kinase 1B (GASK1B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Golgi-associated kinase 1B (GASK1B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Golgi-associated kinase 1B (GASK1B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Golgi-associated kinase 1B (GASK1B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Golgi-associated kinase 1B (GASK1B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Golgi-associated kinase 1B (GASK1B).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Golgi-associated kinase 1B (GASK1B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Golgi-associated kinase 1B (GASK1B).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Golgi-associated kinase 1B (GASK1B).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Golgi-associated kinase 1B (GASK1B).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Golgi-associated kinase 1B (GASK1B).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Golgi-associated kinase 1B (GASK1B).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Golgi-associated kinase 1B (GASK1B).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Golgi-associated kinase 1B (GASK1B).	[16]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Golgi-associated kinase 1B (GASK1B).	[17]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Golgi-associated kinase 1B (GASK1B).	[19]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Golgi-associated kinase 1B (GASK1B).	[20]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Golgi-associated kinase 1B (GASK1B).	[21]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Golgi-associated kinase 1B (GASK1B).	[22]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Golgi-associated kinase 1B (GASK1B).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Golgi-associated kinase 1B (GASK1B).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Golgi-associated kinase 1B (GASK1B).	[25]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Golgi-associated kinase 1B (GASK1B).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Golgi-associated kinase 1B (GASK1B).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Golgi-associated kinase 1B (GASK1B).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Golgi-associated kinase 1B (GASK1B).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Golgi-associated kinase 1B (GASK1B).	[31]

References

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• [3] 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.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] 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.
• [12] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [17] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [20] 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.
• [21] 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.
• [22] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [25] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [26] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.