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Contributor Information

  • Name Andrew Riley ; Barry Potter
  • Institute University of Bath

Tool Details

  • Tool name: HDAC3:SMRT Fluorescent Probe 2-FAM-InsP5 Small Molecule (Tool Compound)
  • Alternate names: HDACs; Histone deacetylases; SMRT; silencing mediator for retinoid or thyroid-hormone receptors; Nuclear receptor co-repressor 2; NCOR2; HDAC:SMRT3; 2-FAM-InsP5; T3 receptor-associating cofactor 1; TRAC-1
  • Molecular formula: C29H32NO27P5.4.5Et3N
  • Tool type: Small molecules
  • Tool sub-type: Fluorescent Probe
  • Molecular weight of the target: 1436 g/mol
  • Application: 2-FAM-InsP5 [2-FAM-Ins(1,3,4,5,6)P5] is a fluorescent derivative of Ins(1,3,4,5,6)P5. 2-FAM-InsP5 activates the HDAC3:SMRT complex in a similar manner to the natural ligand, Ins(1,4,5,6)P4. The binding constant (Kd) for binding of 2-FAM-InsP5 to HDAC3:SMRT measured by a direct binding assay, 0.3 Âą 0.01 ÎźM, was approximately 10-fold lower than the Kdapp for activation of the catalytic activity of HDAC3:SMRT by Ins(1,4,5,6)P4. Utility of 2_FAM-InsP5 as a tool for study of inositol phosphate kinases.
  • Description: Class I histone deacetylase (HDAC) enzymes are involved in epigenetic gene regulation by controlling acetylation of lysine sidechains in histone tails They form a catalytic subunit for other large protein complexes that repress gene expression when targeted to genomic DNA. The Class I HDAC family includes HDACs 1, 2, 3 & 8, however only HDAC3 is recruited exclusively to the SMRT co-repressor complex. Functional and structural studies of HDACs when bound to their cognate corepressors has revealed that the regulation of their activity is controlled intracellularly by inositol phosphates. The molecule, Ins(1,4,5,6)P4, had been found to locate in the binding pocket formed between HDAC3 and SMRT. The transcriptional coregulatory protein SMRT contains several nuclear receptor-interacting domains possessing modulatory functions including several autonomous repression domains. SMRT functions as a repressive coregulatory factor (corepressor) for many transcription factor pathways. SMRT also functions as a platform, facilitating the recruitment of histone deacetylases to the DNA promoters bound by its interacting transcription factors. Targeting HDACS provides promising epigenetic therapies for many diseases including Alzheimer's and spinal muscular atrophy.
  • Research area: Cancer; Drug Discovery & Development; Stem Cell Biology
  • IUPAC: 2-O-(2-(5-fluoresceinylcarboxy)-aminoethyl)-myo-inositol 1,3,4,5,6-pentakisphosphate triethylammonium salt

  • For Research Use Only

Target Details

  • Target molecular weight: 1436 g/mol
  • Primary target: HDAC3:SMRT Complex

Application Details

  • Application: 2-FAM-InsP5 [2-FAM-Ins(1,3,4,5,6)P5] is a fluorescent derivative of Ins(1,3,4,5,6)P5. 2-FAM-InsP5 activates the HDAC3:SMRT complex in a similar manner to the natural ligand, Ins(1,4,5,6)P4. The binding constant (Kd) for binding of 2-FAM-InsP5 to HDAC3:SMRT measured by a direct binding assay, 0.3 Âą 0.01 ÎźM, was approximately 10-fold lower than the Kdapp for activation of the catalytic activity of HDAC3:SMRT by Ins(1,4,5,6)P4. Utility of 2_FAM-InsP5 as a tool for study of inositol phosphate kinases.

Handling

  • Purity: 1436 g/mol
  • Storage conditions: -20°C, protect from light
  • Shipping conditions: Dry Ice

Documentation

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References

  • •  Watson et al. 2016. Nat Commun. 7:11262. PMID: 27109927.