PDH-E1β Inhibitors
Chemical inhibitors of PDH-E1β target various aspects of its activity and regulation within the cell. Radicicol and Novobiocin interact with Hsp90, a chaperone protein that aids in the folding and function of a variety of client proteins, including kinases that phosphorylate PDH-E1β. Their binding disrupts Hsp90's function, potentially leading to the destabilization and decreased activity of these kinases, thereby reducing the phosphorylation and inhibition of PDH-E1β.
Furthermore, Triacsin C inhibits long-chain acyl-CoA synthetase, thereby decreasing the levels of acyl-CoA, which are necessary for the acetylation and inhibition of PDH-E1β. Oxamate acts as a competitive inhibitor of lactate dehydrogenase, which shifts the pyruvate equilibrium towards lactate formation, away from PDH-E1β. By inhibiting lactate dehydrogenase, Oxamate can lead to the accumulation of pyruvate, resulting in a feedback inhibition of PDH-E1β. Similarly, α-Cyano-4-hydroxycinnamate blocks the mitochondrial pyruvate carrier, reducing pyruvate transport into the mitochondria where PDH-E1β operates, thus inhibiting the enzyme by limiting its substrate availability. α-Ketobutyrate competes with pyruvate at the active site of PDH-E1β, preventing the enzyme from catalyzing its normal reaction. Phenylbutyrate, by inhibiting glutamine metabolism, reduces the production of substrates for the TCA cycle, which can lower the activity of PDH-E1β due to reduced substrate flux through the cycle. Monomethyl fumarate inhibits succinate dehydrogenase in the TCA cycle, which may cause an imbalance in the cycle's intermediates that indirectly affects PDH-E1β activity. Gossypol targets various dehydrogenases and could inhibit PDH-E1β by interfering with its dehydrogenase activity. Lastly, Menadione depletes thiol groups through redox cycling, potentially disrupting the catalytic mechanism of thiol-dependent enzymes like PDH-E1β, leading to its inhibition.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Radicicol | 12772-57-5 | sc-200620 sc-200620A | 1 mg 5 mg | $90.00 $326.00 | 13 | |
Radicicol binds to Hsp90, a chaperone protein involved in stabilizing and activating many proteins including kinases that can phosphorylate PDH-E1β. Inhibition of Hsp90 can destabilize these kinases, leading to reduced phosphorylation and thus inhibition of PDH-E1β. | ||||||
Novobiocin | 303-81-1 | sc-362034 sc-362034A | 5 mg 25 mg | $96.00 $355.00 | ||
Novobiocin also targets Hsp90, disrupting its chaperone function. This can prevent the proper folding and function of kinases involved in PDH-E1β regulation, leading to its decreased phosphorylation and inhibition. | ||||||
Triacsin C Solution in DMSO | 76896-80-5 | sc-200574 sc-200574A | 100 µg 1 mg | $149.00 $826.00 | 14 | |
Triacsin C inhibits long-chain acyl-CoA synthetase, reducing the levels of acyl-CoA. Acyl-CoA is necessary for the acetylation of PDH-E1β, which is a modification that can lead to its inhibition. | ||||||
Oxamic acid | 471-47-6 | sc-250620 | 25 g | $145.00 | ||
Oxamate is a competitive inhibitor of lactate dehydrogenase (LDH), which can divert pyruvate away from PDH-E1β. By inhibiting LDH, more pyruvate is available for PDH-E1β, which can lead to an overaccumulation of its substrates and feedback inhibition of the enzyme. | ||||||
α-Cyano-4-hydroxycinnamic acid | 28166-41-8 | sc-254923 | 2 g | $42.00 | 2 | |
This compound inhibits the mitochondrial pyruvate carrier, which is responsible for transporting pyruvate into the mitochondria where PDH-E1β operates. Inhibition of this carrier can decrease the substrate availability for PDH-E1β, leading to its functional inhibition. | ||||||
Sodium phenylbutyrate | 1716-12-7 | sc-200652 sc-200652A sc-200652B sc-200652C sc-200652D | 1 g 10 g 100 g 1 kg 10 kg | $75.00 $163.00 $622.00 $4906.00 $32140.00 | 43 | |
Phenylbutyrate has been shown to inhibit glutamine metabolism. As glutamine metabolism can provide substrates for the TCA cycle, inhibition of this pathway can reduce the flux through PDH-E1β, thus inhibiting its activity. | ||||||
mono-Methyl fumarate | 2756-87-8 | sc-235887 sc-235887A sc-235887B sc-235887C | 1 g 100 g 500 g 1 kg | $27.00 $67.00 $204.00 $341.00 | 1 | |
Monomethyl fumarate inhibits succinate dehydrogenase (SDH), an enzyme in the TCA cycle downstream of PDH-E1β. Inhibition of SDH can lead to TCA cycle disruption, which can indirectly inhibit PDH-E1β by altering the metabolic balance. | ||||||
Gossypol | 303-45-7 | sc-200501 sc-200501A | 25 mg 100 mg | $114.00 $225.00 | 12 | |
Gossypol has been shown to inhibit several dehydrogenases and could potentially inhibit PDH-E1β by interfering with its dehydrogenase activity. | ||||||
Vitamin K3 | 58-27-5 | sc-205990B sc-205990 sc-205990A sc-205990C sc-205990D | 5 g 10 g 25 g 100 g 500 g | $25.00 $35.00 $46.00 $133.00 $446.00 | 3 | |
Menadione can act as a redox-cycling agent, depleting thiol groups. This depletion can affect the lipoamide-dependent enzymes such as PDH-E1β by interfering with its catalytic mechanism and leading to functional inhibition. | ||||||