UGT1A5 Inhibitors
UGT1A5 inhibitors represent a category of chemicals that interact with the UDP-glucuronosyltransferase 1A5 enzyme, resulting in the diminishment of its glucuronidation activity. These inhibitors can achieve their effect through various mechanisms, including competitive inhibition, where they directly compete with the natural substrates of UGT1A5, thereby hindering these substrates from accessing the active site of the enzyme. Some inhibitors can bind non-competitively, altering the enzyme's conformation and thus its activity without directly competing with the substrates for the active site. The inhibition of UGT1A5 has consequential effects on the enzyme's capacity to conjugate glucuronic acid to a diverse array of substrates, including hormones, xenobiotics, and toxic substances, thus influencing the solubility, reactivity, and excretion of these compounds.
The inhibition of UGT1A5 by these chemicals is indicative of their ability to interact with the enzyme's active site or allosteric sites in a manner that impairs substrate processing. The inhibitors range from endogenous compounds, such as steroid hormones, to various agents including antifungal drugs, kinase inhibitors, and antiretrovirals. Each inhibitor, while differing in structure and primary pharmacological action, shares the common feature of modulating the activity of UGT1A5. This modulation occurs via direct binding to the active site, conformational alteration of the enzyme, or competition for substrate binding, all of which lead to a decrease in the glucuronidation activity of UGT1A5. The detailed mechanisms of inhibition vary, reflecting the diverse chemical structures and interactions that these molecules exhibit with UGT1A5.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Fluconazole | 86386-73-4 | sc-205698 sc-205698A | 500 mg 1 g | $54.00 $84.00 | 14 | |
Fluconazole is a triazole antifungal agent known to inhibit UGT enzymes. It interferes with the UGT1A5 activity by binding to the enzyme's active site, thereby obstructing the access of the enzyme's natural substrates. As a result, the glucuronidation process facilitated by UGT1A5 is inhibited. | ||||||
Ketoconazole | 65277-42-1 | sc-200496 sc-200496A | 50 mg 500 mg | $63.00 $265.00 | 21 | |
Ketoconazole, an imidazole antifungal agent, inhibits cytochrome P450 enzymes and is also reported to inhibit UGTs including UGT1A5. It acts by directly interacting with the active site of UGT1A5, impeding substrate access and thus decreasing the glucuronidation activity of the enzyme. | ||||||
Atazanavir | 198904-31-3 | sc-207305 | 5 mg | $292.00 | 7 | |
Atazanavir, an antiretroviral agent in research, is shown to inhibit UGT1A5. It binds to the enzyme and alters its conformation, leading to reduced binding of substrates and subsequent inhibition of the glucuronidation process that UGT1A5 facilitates. | ||||||
Gemfibrozil | 25812-30-0 | sc-204764 sc-204764A | 5 g 25 g | $66.00 $267.00 | 2 | |
Gemfibrozil, a fibric acid derivative, is documented to inhibit UGT enzymes. It binds to UGT1A5 and modifies its active site, hindering the binding and processing of glucuronic acid to substrates. This interaction diminishes the catalytic efficiency of UGT1A5, leading to an inhibition of the glucuronidation reactions it normally performs. | ||||||
Sorafenib | 284461-73-0 | sc-220125 sc-220125A sc-220125B | 5 mg 50 mg 500 mg | $57.00 $100.00 $250.00 | 129 | |
Sorafenib, a kinase inhibitor, has been observed to inhibit UGTs. It competes with UGT1A5's natural substrates for binding sites, thus inhibiting the enzyme's normal function in glucuronidation. This interference affects the enzymatic activity of UGT1A5 by decreasing its capacity to bind and process its substrates through glucuronidation. | ||||||
Ritonavir | 155213-67-5 | sc-208310 | 10 mg | $124.00 | 7 | |
Ritonavir, primarily an HIV protease inhibitor, also exhibits inhibitory effects on UGT1A5. It competes with endogenous substrates for the enzyme's active site, which diminishes the UGT1A5-mediated glucuronidation. | ||||||
Nilotinib | 641571-10-0 | sc-202245 sc-202245A | 10 mg 25 mg | $209.00 $413.00 | 9 | |
Nilotinib, a selective tyrosine kinase inhibitor, is also noted for its ability to inhibit UGT1A5. Its binding to the active site of UGT1A5 decreases the affinity for natural substrates, thereby impairing the glucuronidation process carried out by the enzyme. | ||||||
Pazopanib | 444731-52-6 | sc-396318 sc-396318A | 25 mg 50 mg | $130.00 $182.00 | 2 | |
Pazopanib, a multi-targeted receptor tyrosine kinase inhibitor, has inhibitory effects on UGT enzymes. It interacts with UGT1A5, possibly by allosteric effects or direct competition with the active site, leading to decreased enzyme activity. | ||||||
Dasatinib | 302962-49-8 | sc-358114 sc-358114A | 25 mg 1 g | $70.00 $145.00 | 51 | |
Dasatinib, another tyrosine kinase inhibitor, can inhibit UGT1A5. By binding non-competitively to the enzyme, dasatinib alters UGT1A5's structure, which decreases its activity and the efficiency of the glucuronidation process it facilitates. | ||||||