Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0VRZA6)

• DOT Name: SAFB-like transcription modulator (SLTM)
• Synonyms: Modulator of estrogen-induced transcription
• Gene Name: SLTM
• Related Disease:
  Neoplasm
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Anaplastic astrocytoma
  Fibrosarcoma
  Glioblastoma multiforme
• UniProt ID: SLTM_HUMAN
• Pfam ID: PF00076 ; PF02037
• Sequence:
  MAAATGAVAASAASGQAEGKKITDLRVIDLKSELKRRNLDITGVKTVLISRLKQAIEEEG
  GDPDNIELTVSTDTPNKKPTKGKGKKHEADELSGDASVEDDAFIKDCELENQEAHEQDGN
  DELKDSEEFGENEEENVHSKELLSAEENKRAHELIEAEGIEDIEKEDIESQEIEAQEGED
  DTFLTAQDGEEEENEKDIAGSGDGTQEVSKPLPSEGSLAEADHTAHEEMEAHTTVKEAED
  DNISVTIQAEDAITLDFDGDDLLETGKNVKITDSEASKPKDGQDAIAQSPEKESKDYEMN
  ANHKDGKKEDCVKGDPVEKEARESSKKAESGDKEKDTLKKGPSSTGASGQAKSSSKESKD
  SKTSSKDDKGSTSSTSGSSGSSTKNIWVSGLSSNTKAADLKNLFGKYGKVLSAKVVTNAR
  SPGAKCYGIVTMSSSTEVSRCIAHLHRTELHGQLISVEKVKGDPSKKEMKKENDEKSSSR
  SSGDKKNTSDRSSKTQASVKKEEKRSSEKSEKKESKDTKKIEGKDEKNDNGASGQTSESI
  KKSEEKKRISSKSPGHMVILDQTKGDHCRPSRRGRYEKIHGRSKEKERASLDKKRDKDYR
  RKEILPFEKMKEQRLREHLVRFERLRRAMELRRRREIAERERRERERIRIIREREERERL
  QRERERLEIERQKLERERMERERLERERIRIEQERRKEAERIAREREELRRQQQQLRYEQ
  EKRNSLKRPRDVDHRRDDPYWSENKKLSLDTDARFGHGSDYSRQQNRFNDFDHRERGRFP
  ESSAVQSSSFERRDRFVGQSEGKKARPTARREDPSFERYPKNFSDSRRNEPPPPRNELRE
  SDRREVRGERDERRTVIIHDRPDITHPRHPREAGPNPSRPTSWKSEGSMSTDKRETRVER
  PERSGREVSGHSVRGAPPGNRSSASGYGSREGDRGVITDRGGGSQHYPEERHVVERHGRD
  TSGPRKEWHGPPSQGPSYHDTRRMGDGRAGAGMITQHSSNASPINRIVQISGNSMPRGSG
  SGFKPFKGGPPRRF
• Function: When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Anaplastic astrocytoma	DISSBE0K	Strong	Biomarker	[2]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of SAFB-like transcription modulator (SLTM).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of SAFB-like transcription modulator (SLTM).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of SAFB-like transcription modulator (SLTM).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of SAFB-like transcription modulator (SLTM).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SAFB-like transcription modulator (SLTM).	[6]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of SAFB-like transcription modulator (SLTM).	[8]

References

• [1] Nonclinical evaluation of the serum pharmacodynamic biomarkers HGF and shed MET following dosing with the anti-MET monovalent monoclonal antibody onartuzumab.Mol Cancer Ther. 2014 Feb;13(2):540-52. doi: 10.1158/1535-7163.MCT-13-0494. Epub 2013 Nov 20.
• [2] RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas.Genome Res. 2014 Nov;24(11):1765-73. doi: 10.1101/gr.165126.113. Epub 2014 Aug 18.
• [3] Methioninase gene therapy of human cancer cells is synergistic with recombinant methioninase treatment.Cancer Res. 2000 May 15;60(10):2696-702.
• [4] Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer's disease.Mol Neurodegener. 2016 Jan 12;11:3. doi: 10.1186/s13024-016-0071-x.
• [5] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [6] 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.
• [7] 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.
• [8] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.
• [9] 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.