HSPA6 Inhibitors
HSPA6 inhibitors encompass a group of chemical entities designed to selectively interfere with the function of the Heat Shock 70kDa Protein 6 (HSPA6), which is a part of the Heat Shock Protein 70 (HSP70) family. HSPA6, like other members of this family, acts as a molecular chaperone that assists in the correct folding of nascent or stress-accumulated misfolded proteins, as well as in the prevention of protein aggregation. The expression of HSPA6 is typically stress-induced, with its upregulation being a cellular response to a variety of stressful stimuli such as heat shock, heavy metals, and oxidative stress. Inhibitors targeting HSPA6 aim to modulate this cellular stress response by binding to the protein, thereby potentially altering its chaperone activity. Such inhibition could impact the protein's ATPase activity, substrate binding, or its interaction with co-chaperones, which in turn may influence the protein's ability to assist in the folding and stabilization of other proteins within the cell. The precise mode of action of HSPA6 inhibitors might involve the binding to the N-terminal nucleotide-binding domain or the C-terminal substrate-binding domain, effectively hampering the ATPase cycle that is essential for the chaperone's function.
The exploration and development of HSPA6 inhibitors typically start with high-throughput screening strategies to identify compounds that exhibit inhibitory effects on the chaperone's activity. Once candidate inhibitors are identified, they undergo a series of biochemical and biophysical assays to confirm their activity and to elucidate their mechanism of action. Techniques such as ATPase assays can help determine the impact of the inhibitors on the enzyme's catalytic activity, while surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) can provide detailed insights into the binding kinetics and thermodynamics between HSPA6 and the inhibitors. To gain a deeper understanding of how these inhibitors interact with HSPA6 at an atomic level, structural studies using X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy may be conducted.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Quercetin | 117-39-5 | sc-206089 sc-206089A sc-206089E sc-206089C sc-206089D sc-206089B | 100 mg 500 mg 100 g 250 g 1 kg 25 g | $11.00 $17.00 $110.00 $250.00 $936.00 $50.00 | 33 | |
Quercetin is a flavonoid that can stabilize heat shock factor 1 (HSF1) in its inactive form. Since HSF1 is responsible for upregulating HSPA6 in response to stress, quercetin can lead to a decrease in HSPA6 expression. | ||||||
Geldanamycin | 30562-34-6 | sc-200617B sc-200617C sc-200617 sc-200617A | 100 µg 500 µg 1 mg 5 mg | $39.00 $59.00 $104.00 $206.00 | 8 | |
Geldanamycin binds to HSP90 and inhibits its function. HSP90 is involved in the correct folding of proteins and the stabilization of HSF1. By inhibiting HSP90, geldanamycin can promote the degradation of misfolded proteins and attenuate the induction of HSP70 family proteins like HSPA6. | ||||||
17-AAG | 75747-14-7 | sc-200641 sc-200641A | 1 mg 5 mg | $67.00 $156.00 | 16 | |
17-AAG is a derivative of geldanamycin and also targets HSP90. By binding to HSP90, it can inhibit its activity, which in turn can decrease HSPA6 expression due to reduced stabilization of proteins and HSF1 activity. | ||||||
17-DMAG | 467214-20-6 | sc-202005 | 1 mg | $205.00 | 8 | |
17-DMAG is another analog of geldanamycin with similar activity. It binds to HSP90 and inhibits its chaperone function, potentially decreasing the expression of stress-induced proteins like HSPA6. | ||||||
Triptolide | 38748-32-2 | sc-200122 sc-200122A | 1 mg 5 mg | $90.00 $204.00 | 13 | |
Triptolide is a diterpene triepoxide that can inhibit the transcription of heat shock proteins by preventing the binding of HSF1 to heat shock elements (HSE) on DNA. This inhibition can result in decreased expression of HSPA6. | ||||||
(−)-Epigallocatechin Gallate | 989-51-5 | sc-200802 sc-200802A sc-200802B sc-200802C sc-200802D sc-200802E | 10 mg 50 mg 100 mg 500 mg 1 g 10 g | $43.00 $73.00 $126.00 $243.00 $530.00 $1259.00 | 11 | |
EGCG is the main catechin found in green tea and can modulate HSP70 family proteins expression by affecting HSF1 activity. This can lead to reduced expression of HSPA6. | ||||||
Radicicol | 12772-57-5 | sc-200620 sc-200620A | 1 mg 5 mg | $92.00 $333.00 | 13 | |
Radicicol is a potent HSP90 inhibitor that binds to the ATPase domain of HSP90, thereby inhibiting its function and affecting the expression of HSP70 family proteins such as HSPA6. | ||||||
Withaferin A | 5119-48-2 | sc-200381 sc-200381A sc-200381B sc-200381C | 1 mg 10 mg 100 mg 1 g | $130.00 $583.00 $4172.00 $20506.00 | 20 | |
Withaferin A is a steroidal lactone from Withania somnifera that can disrupt proteostasis by inhibiting the proteasomal degradation of misfolded proteins. This can overload the protein quality control system and reduce the cellular capacity to upregulate heat shock proteins like HSPA6. | ||||||
Celastrol, Celastrus scandens | 34157-83-0 | sc-202534 | 10 mg | $158.00 | 6 | |
Celastrol is a quinone methide triterpene that can activate HSF1 but paradoxically leads to the inhibition of the heat shock response. This can result in decreased expression of HSPA6. | ||||||
Puromycin dihydrochloride | 58-58-2 | sc-108071 sc-108071B sc-108071C sc-108071A | 25 mg 250 mg 1 g 50 mg | $42.00 $214.00 $832.00 $66.00 | 394 | |
Puromycin is an aminonucleoside antibiotic that causes premature chain termination during protein synthesis. This can lead to the accumulation of misfolded proteins and subsequent cellular stress, which may overwhelm the protein folding machinery and decrease the cellular capacity to induce HSPA6. | ||||||