For research use only. Not for therapeutic Use.
HSF1A is a cell-permeable activator of heat shock transcription factor 1 (HSF1)[1]. HSF1A also acts as a specific inhibitor of TRiC/CCT. Chaperonin TCP-1 ring complex (TRiC)/chaperonin containing TCP-1 (CCT) plays a pivotal role in toxin translocation and/or refolding[4].
HSF1A protects cells from stress-induced apoptosis, binds TRiC subunits and inhibits TRiC activity without perturbation of ATP hydrolysis. Genetic inactivation or depletion of the TRiC complex results in human HSF1 activation and HSF1A inhibits the direct interaction between purified TRiC and HSF1 in vitro. Moreover, fluorescence anisotropy experiments using FITC coupled to HSF1A demonstrates that HSF1A-FITC binds to a purified Tcp1 subunit of TRiC with an affinity of approximately 600 nM. This is validated qualitatively via titration of purified Tcp1 into binding reactions containing 500 nM Biotin or HSF1A-Biotin[1]. Quantification by counting the number of cell containing aggregates as a function of the total number of cells reveals that at HSF1A concentrations as low as 2 µM, a reduced number of aggregate-containing cells are observed. The fraction of cells containing aggregates continued to decrease in a dose-dependent manner such that pretreatment with 12 µM HSF1A resulta in ~20% of the cells exhibiting aggregates visible by fluorescence microscopy[2].
HSF1A enhances HSF1 activity, stabilizes HSF1 expression and minimizes Doxorubicin (DOX)-induced cardiac damage. WKY rats are challenged with DOX (accumulated dose: 30 mg/kgw), and DOX combined with HSF1A (100 mg/kgw/day). Supplementation with HSF1A significantly elevates cardiac functions back to the levels of the control group. HSF1A has been shown to stimulate human HSF1 nuclear translocation, elevate protein chaperone expression and ameliorate protein misfolding and cell death in a neurodegenerative disease model. The echocardiographic results show that HSF1A also alleviates DOX-induced failures in cardiac function[3].
| Catalog Number | I012569 |
| CAS Number | 1196723-93-9 |
| Synonyms | 4-ethyl-N-(2-phenyl-5-thiophen-2-ylpyrazol-3-yl)benzenesulfonamide |
| Molecular Formula | C21H19N3O2S2 |
| Purity | ≥95% |
| InChI | InChI=1S/C21H19N3O2S2/c1-2-16-10-12-18(13-11-16)28(25,26)23-21-15-19(20-9-6-14-27-20)22-24(21)17-7-4-3-5-8-17/h3-15,23H,2H2,1H3 |
| InChIKey | KJTITGSAONQVPY-UHFFFAOYSA-N |
| SMILES | CCC1=CC=C(C=C1)S(=O)(=O)NC2=CC(=NN2C3=CC=CC=C3)C4=CC=CS4 |
| Reference | [1]. Neef DW, et al. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell Rep. 2014 Nov 6;9(3):955-66. [2]. Neef DW, et al. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biol. 2010 Jan 19;8(1):e1000291. [3]. Huang CY, et al. Doxorubicin attenuates CHIP-guarded HSF1 nuclear translocation and protein stability to trigger IGF-IIR-dependent cardiomyocyte death. Cell Death Dis. 2016 Nov 3;7(11):e2455. [4]. Marcus Steinemann, et al. The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B. Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):9580-9585. |
