Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWVL31L)

DOT Name DmX-like protein 1 (DMXL1)
Synonyms X-like 1 protein
Gene Name DMXL1
Related Disease
Alzheimer disease ( )
Astrocytoma ( )
Glioblastoma multiforme ( )
Glaucoma/ocular hypertension ( )
Glioma ( )
Malignant glioma ( )
Mixed glioma ( )
UniProt ID
DMXL1_HUMAN
Pfam ID
PF12234 ; PF00400
Sequence
MNLHQVLTGAVNPGDHCFSVGSIGDQRFTAYASGCDIVILGSDFERLQIIPGAKHGNIQV
GCVDCSMQQGKIAASYGNVISIFEPVNLPKQKKNLELYSQWQKSGQFFLESIAHNITWDP
TGSRLLTGSSYLQLWSNTNLEKPTEDENLNKTDLNFGDWKCIWHCKTASQVHLMKFSPDG
EFFATAGKDDCLLKVWYNVENWRTAVTSPDGSSEKQSQGEIDFSFVYLAHPRAVNGFSWR
KTSKYMPRASVCNVLLTCCKDNVCRLWVETFLPNDCLLYGGDCSHWTESINLTNNFKRNA
SSKERVQNALEVNLRHFRRGRRRSLALVAHTGYLPHQQDPHHVHRNTPLHANALCHFHIA
ASINPATDIPLLPSITSLSLNENEEKTGPFVVHWLNNKELHFTLSMEVFLQQLRKSFEQP
SSEASVEDSNQADVKSDEETDDGVDDLKINPEKKELGCDKMVPNSSFTSLSSAAIDHQIE
VLLSEWSKNADMLFSIHPMDGSLLVWHVDWLDEYQPGMFRQVQVSFVSRIPVAFPTGDAN
SLCKSIMMYACTKNVDLAIQQGKQKPSGLTRSTSMLISSGHNKSSNSLKLSIFTPNVMMI
SKHADGSLNQWLVSFAEESAFSTVLSISHKSRYCGHRFHLNDLACHSVLPLLLTTSHHNA
LRTPDVDNPEQPFDALNIEECSLTQQNKSTVDVAFQDPSAVYSELILWRVDPVGPLSFSG
GVSELARINSLHVSAFSNVAWLPTLIPSYCLGAYCNSPSACFVASDGQYLRLYEAVIDAK
KLLSELSNPEISKYVGEVFNIVSQQSTARPGCIIALDPITKLHGRKTQLLHVFEEDFILN
NLEKKSLGKDSILSNAGSSPNGFSEKFYLIVIECTQDNRSLLHMWNLHLKSIPVSLDEKV
DTKLSEAVWQPEEHYSSSPEKILSPFSQKYQACRANLQSTSRLTLFSEMVYSQELHLPEG
VEIISIKPSAGHLSSSSIYPACSAPYLLATSCSDEKVRFWRCRVTDGESATSKNGKIDLA
YIWEEWPLLIEDGLQSNSSITVPGRPVEVSCAHTNRLAVAYKQPASNSRSSQDFVMHVSI
FECESTGGSCWVLEQTIHLDELSTVLDSGISVDSNLVAYNKQDMYLSSKENITSNTKHLV
HLDWMSREDGSHILTVGIGSKLFMYGPLAGKVQDQTGKETLAFPLWESTKVVPLSKFVLL
RSVDLVSSVDGSPPFPVSLSWVRDGILVVGMDCEMHVYCQWQPSSKQEPVITDSYSGSTP
SITSLIKQSNSSSGLHPPKKTLTRSMTSLAQKICGKKTAFDPSVDMEDSGLFEAAHVLSP
TLPQYHPLQLLELMDLGKVRRAKAILSHLVKCIAGEVVALNEAESNHERRLRSLTISASG
STTRDPQAFNKAENTDYTEIDSVPPLPLYALLAADDDSCYSSLEKSSNESTLSKSNQLSK
ESYDELFQTQLLMTDTHMLETDEENTKPRVIDLSQYSPTYFGPEHAQVLSGHLLHSSLPG
LSRMEQMSLMALADTIATTSTDIGESRDRSQGGETLDECGLKFLLAVRLHTFLTTSLPAY
RAQLLHQGLSTSHFAWAFHSVAEEELLNMLPAMQKDDPTWSELRAMGVGWWVRNTRILRK
CIEKVAKAAFYRKNDPLDAAIFYLAMKKKAVIWGLYRAEKNTRMTQFFGHNFEDERWRKA
ALKNAFSLLGKQRFEHSAAFFLLAGCLRDAIEVCLEKLNDIQLALVIARLYESEFDTSAA
YKSILRKKVLGIDSPVSELCSLNINMHHDPFLRSMAYWILEDYSGALETLIKQPIRENDD
QVLSASNPTVFNFYNYLRTHPLLLRRHFGSSDTFSTHMSLTGKSGLAGTINLSERRLFFT
TASAHLKAGCPMLALEVLSKMPKVIKKTRPFYRASSFLDTSKDCSPSSPLKLDAREDKSS
AVDWSQSLINGFGSSSEGSSEKQSNSTLSFDWSQPSVVFQDDSLELKWDSDNDEENEDVP
ISMKELKPLQRKTDKKLDDISSNYTESFSTLDENDLLNPSEDIIAVQLKFRACLKILTVE
LRTLSTGYEIDGGKLRYQLYHWLEKEVIALQRTCDFCSDAEELQSAFGRNEDEFGLNEDA
EDLPHQTKVKQLRENFQEKRQWLLKYQSLLRMFLSYCILHGSHGGGLASVRMELILLLQE
SQQETSEPLFSSPLSEQTSVPLLFACTANAKTVVANPLLHLSNLTHDILHAIINFDSPPH
PDIQSNKVYVMHTLAASLSACIYQCLCGSHNYSSFQTNQFTGMVYQTVLLPHRPSLKTGS
LDEALTPNTSPAQWPGITCLIRLLNSSGEEAQSGLTVLLCEILTAVYLSLFIHGLATHSS
NELFRIVAHPLNEKMWSAVFGGGAHVPSKEQTHSKTLPVSSLVEEGEKQNKRFRPSKMSC
RESAPLTPSSAPVSQESLAVKEKFIPPELSIWDYFIAKPFLPSSQSRAEYDSEESLGSDD
DDNDDDDDVLASDFHLQEHSNSNSYSWSLMRLAMVQLVLNNLKTFYPFAGHDLAELPVSS
PLCHAVLKTLQCWEQVLLRRLEIHGGPPQNYIASHTAEESLSAGPAILRHKALLEPTNTP
FKSKHHLALSVKRLWQYLVKQEEIQETFIKNIFTKKRCLNEIEADLGYPGGKARIIHKES
DIITAFAVNKANRNCIAIASSHDVQELDVSGILATQVYTWVDDDIEVETKGSEDFLVIHA
RDDLTAVQGTTPYTHSNPGTPINMPWLGSTQTGRGASVMIKKAINNVRRMTSHPTLPYYL
TGAQDGSVRMFEWGHSQQITCFRSGGNSRVTRMRFNYQGNKFGIVDADGYLSLYQTNWKC
CPVTGSMPKPYLTWQCHNKTANDFVFVSSSSLIATAGLSTDNRNVCLWDTLVAPANSLVH
AFTCHDSGATVLAYAPKHQLLISGGRKGFTYVFDLCQRQQRQLFQSHDSPVKAVAVDPTE
EYFVTGSAEGNIKIWSLSTFGLLHTFVSEHARQSIFRNIGTGVMQIETGPANHIFSCGAD
GTMKMRILPDQFSPLNEVLKNDVKFML
Tissue Specificity Expressed in bone, breast, eye, foreskin, heart, parathyroid, small intestine, testis, tonsils, placenta and uterus.
KEGG Pathway
Lysosome (hsa04142 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Genetic Variation [1]
Astrocytoma DISL3V18 Disputed Altered Expression [2]
Glioblastoma multiforme DISK8246 Disputed Altered Expression [2]
Glaucoma/ocular hypertension DISLBXBY Limited Genetic Variation [3]
Glioma DIS5RPEH Limited Biomarker [2]
Malignant glioma DISFXKOV Limited Biomarker [2]
Mixed glioma DIS64UY3 Limited Biomarker [2]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
25 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of DmX-like protein 1 (DMXL1). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of DmX-like protein 1 (DMXL1). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DmX-like protein 1 (DMXL1). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of DmX-like protein 1 (DMXL1). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of DmX-like protein 1 (DMXL1). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of DmX-like protein 1 (DMXL1). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of DmX-like protein 1 (DMXL1). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of DmX-like protein 1 (DMXL1). [5]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of DmX-like protein 1 (DMXL1). [11]
Panobinostat DM58WKG Approved Panobinostat increases the expression of DmX-like protein 1 (DMXL1). [11]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of DmX-like protein 1 (DMXL1). [12]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of DmX-like protein 1 (DMXL1). [13]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of DmX-like protein 1 (DMXL1). [14]
ACYLINE DM9GRTK Phase 2 ACYLINE increases the expression of DmX-like protein 1 (DMXL1). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of DmX-like protein 1 (DMXL1). [16]
Scriptaid DM9JZ21 Preclinical Scriptaid increases the expression of DmX-like protein 1 (DMXL1). [11]
Oxamflatin DM1TG3C Terminated Oxamflatin increases the expression of DmX-like protein 1 (DMXL1). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of DmX-like protein 1 (DMXL1). [18]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of DmX-like protein 1 (DMXL1). [19]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of DmX-like protein 1 (DMXL1). [20]
KOJIC ACID DMP84CS Investigative KOJIC ACID decreases the expression of DmX-like protein 1 (DMXL1). [22]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of DmX-like protein 1 (DMXL1). [10]
Apicidin DM83WVF Investigative Apicidin increases the expression of DmX-like protein 1 (DMXL1). [11]
DZNep DM0JXBK Investigative DZNep decreases the expression of DmX-like protein 1 (DMXL1). [11]
Octanedioic acid bis-hydroxyamide DMJNQ9K Investigative Octanedioic acid bis-hydroxyamide increases the expression of DmX-like protein 1 (DMXL1). [11]
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⏷ Show the Full List of 25 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of DmX-like protein 1 (DMXL1). [17]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the phosphorylation of DmX-like protein 1 (DMXL1). [21]
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References

1 Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.Alzheimers Dement. 2014 Jan;10(1):45-52. doi: 10.1016/j.jalz.2013.01.008. Epub 2013 Mar 25.
2 Identification of novel genes associated with astrocytoma progression using suppression subtractive hybridization and real-time reverse transcription-polymerase chain reaction.Int J Cancer. 2006 Nov 15;119(10):2330-8. doi: 10.1002/ijc.22108.
3 Copy number variations and primary open-angle glaucoma.Invest Ophthalmol Vis Sci. 2011 Sep 9;52(10):7122-33. doi: 10.1167/iovs.10-5606. Print 2011.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
6 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.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
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 Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
12 Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
13 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
14 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.
15 Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41.
16 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.
17 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.
18 Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
19 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.
20 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
21 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
22 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.