Details of Drug Off-Target (DOT)

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

• DOT Name: Pleckstrin homology-like domain family B member 3 (PHLDB3)
• Gene Name: PHLDB3
• UniProt ID: PHLB3_HUMAN
• Pfam ID: PF00169
• Sequence:
  MGTRSSPEEGTPPPLVPECDVEVQPQGHPEESREQEASEVLAEPSSRGGAEQQAEEEEVG
  EGSSTESSRDAPEATPPIAMAATPPASTSSREGVRGAARRLQGQQLEALTRVALMEQRVK
  ELQRQRKELRIEMEVEVALLRGELAGERVAARREEEQLRELLEQQAASEQRGRQQREQEQ
  RRLSQERDRLEGLRQRLRKAQGQLDSQPEDQRERLLQGVQEMREQLDVAQRAYEDLEFQQ
  LERESRQEEEDRDSPGPQVPDPKVQELQASMAQHRRGALQHRIRVLEEQLKSLGEQMAAE
  SRGLSRKKEEALQALSQERSRLLELNCLQGTPGGDFSEPNPALTKLLFTQKTDRQLLVLQ
  DAVAHSAATPTSSCLFSVHSSLQGSIGLQRTGSLPRKRGERGSQRGSPRPLSFHCTESLE
  ASALPPAVGDSGRYPLYQLLNCGRGNSCGAIHPDIAHMERLLQQAMAERERLLKAREGTR
  RGTEGSSGPAVPAITAPPTPPHPPGPRILDLRQHLEGWGHNPENCPHVQVSGCCCRGPLV
  KMGGRIKTWRKRWFCFDRQARRLAYYADKEETKLKGVIYFQAIEEVYYDHLRCAFKSPNP
  RLTFCVKTYERLFYMVAPSPEAMRIWMDVIVTAADENHAP

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Pleckstrin homology-like domain family B member 3 (PHLDB3).	[1]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Pleckstrin homology-like domain family B member 3 (PHLDB3).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pleckstrin homology-like domain family B member 3 (PHLDB3).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Pleckstrin homology-like domain family B member 3 (PHLDB3).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Pleckstrin homology-like domain family B member 3 (PHLDB3).	[7]

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 decreases the phosphorylation of Pleckstrin homology-like domain family B member 3 (PHLDB3).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Pleckstrin homology-like domain family B member 3 (PHLDB3).	[5]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.