UGT1A3 Inhibitors
UGT1A3 inhibitors are a diverse group of chemicals that share the common feature of reducing the glucuronidation activity of UGT1A3, a UDP-glucuronosyltransferase. This enzyme plays a crucial role in the metabolism of bilirubin and various endogenous and exogenous compounds by adding glucuronic acid, which makes these compounds more water-soluble and thus easier to excrete. Inhibitors of UGT1A3 act by various mechanisms: competitive inhibition, where the inhibitor competes with natural substrates for binding to the active site of the enzyme; non-competitive inhibition, where the inhibitor binds to an allosteric site of the enzyme, changing its conformation and reducing its activity; and downregulation of gene expression, which leads to reduced enzyme synthesis. Some of these inhibitors, such as atazanavir and gemfibrozil, can affect UGT1A3 activity indirectly through their influence on other metabolic pathways that interact with the glucuronidation process, such as the competition for bilirubin binding in the case of atazanavir or the modulation of gene expression by gemfibrozil.
The action of UGT1A3 inhibitors is important in the context of understanding the metabolism of various compounds within the liver. Since UGT1A3 is responsible for the detoxification and solubilization of several harmful substances, inhibitors can significantly affect the processing of these substances. For instance, inhibitors like probenecid reduce the substrate availability for UGT1A3 by blocking the uptake of compounds into hepatocytes, where UGT1A3 performs its function. Others, such as piperine and curcumin, interact directly with the enzyme to hinder it from acting on its substrates. Additionally, ketoprofen and fluconazole, can inhibit UGT1A3 by competing with the enzyme's natural substrates, thus altering the metabolism of drugs and other compounds within the liver. The regulation of UGT1A3 is complex, with multiple chemicals capable of inhibiting its activity through different biochemical interactions and pathways.
SEE ALSO...
Items 1 to 10 of 11 total
Display:
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Atazanavir | 198904-31-3 | sc-207305 | 5 mg | $292.00 | 7 | |
Atazanavir is a specific inhibitor of HIV-1 protease that affects the processing of viral polyproteins, leading to non-infectious virus particles. By inhibiting this enzyme, atazanavir indirectly affects the metabolic pathways within hepatocytes, leading to elevated bilirubin levels due to competition with UGT1A3 for the bilirubin substrate, thus inhibiting UGT1A3's ability to glucuronidate bilirubin. | ||||||
Gemfibrozil | 25812-30-0 | sc-204764 sc-204764A | 5 g 25 g | $66.00 $267.00 | 2 | |
Gemfibrozil is a peroxisome proliferator-activated receptor alpha (PPARα) agonist which can downregulate UGT1A3 expression by influencing the transcriptional regulation of the UGT1A3 gene. This leads to decreased glucuronidation activity of UGT1A3, as the enzyme's expression is reduced in hepatocytes. | ||||||
Probenecid | 57-66-9 | sc-202773 sc-202773A sc-202773B sc-202773C | 1 g 5 g 25 g 100 g | $28.00 $39.00 $100.00 $277.00 | 28 | |
Probenecid competitively inhibits various organic anion transporters and by this action, can reduce the substrate availability to UGT1A3. With decreased uptake of substrates into hepatocytes where UGT1A3 is expressed, the glucuronidation activity of UGT1A3 is reduced. | ||||||
Ketoprofen | 22071-15-4 | sc-205359 sc-205359A | 5 g 25 g | $126.00 $339.00 | 2 | |
Ketoprofen can modulate the hepatic drug-metabolizing enzymes, including UGTs, leading to altered UGT1A3 activity due to competitive inhibition, as it is a substrate for this enzyme. When competing for the same active site, ketoprofen can reduce the metabolism of other potential UGT1A3 substrates. | ||||||
Piperine | 94-62-2 | sc-205809 sc-205809A | 5 g 25 g | $37.00 $146.00 | 3 | |
Piperine modulates UGT1A3 by binding to the active site, preventing the glucuronidation of other substrates by UGT1A3. This non-substrate inhibitor alters the function of UGT1A3 by direct binding, leading to a decrease in UGT1A3-mediated metabolism of endogenous and exogenous compounds. | ||||||
Curcumin | 458-37-7 | sc-200509 sc-200509A sc-200509B sc-200509C sc-200509D sc-200509F sc-200509E | 1 g 5 g 25 g 100 g 250 g 1 kg 2.5 kg | $37.00 $69.00 $109.00 $218.00 $239.00 $879.00 $1968.00 | 47 | |
Curcumin interacts directly with the enzyme, resulting in the suppression of UGT1A3-mediated glucuronidation. The compound's inhibitory effect is due to its direct interaction with the catalytic site of the enzyme, preventing the conjugation of UGT1A3's natural substrates. | ||||||
Fluconazole | 86386-73-4 | sc-205698 sc-205698A | 500 mg 1 g | $54.00 $84.00 | 14 | |
Fluconazole, an antifungal agent, is known to inhibit cytochrome P450 enzymes and can modulate UGT enzymes' activity. The inhibition is presumed to occur through competitive inhibition, as fluconazole and UGT1A3 substrates may share overlapping binding sites. This leads to a reduction in UGT1A3 activity. | ||||||
Phenylbutazone | 50-33-9 | sc-204843 | 5 g | $32.00 | 1 | |
Phenylbutazone has been shown to inhibit UGT enzymes, including UGT1A3. It interacts with the active site of UGT1A3 and can displace other substrates from this region, leading to a reduction in UGT1A3 activity. This direct interaction inhibits the normal function of UGT1A3. | ||||||
(±)-Sulfinpyrazone | 57-96-5 | sc-202822 sc-202822A | 1 g 5 g | $42.00 $94.00 | 2 | |
Sulfinpyrazone competitively inhibits UGT enzymes. Its inhibitory effect on UGT1A3 results from the competition for the enzyme's active site, reducing the glucuronidation of other substrates by UGT1A3 and thus decreasing the enzyme's activity. | ||||||
Ciprofibrate | 52214-84-3 | sc-204689 sc-204689A | 25 mg 100 mg | $58.00 $172.00 | ||
Ciprofibrate activates PPARα and through this activation can modulate the expression of UGT1A3. It leads to altered transcription and decreased expression of UGT1A3, resulting in diminished enzyme activity and reduced glucuronidation of substrates normally metabolized by UGT1A3. | ||||||