THTPA Inhibitors
Chemical inhibitors of thiamine triphosphatase (THTPA) include a range of compounds that interfere with folate metabolism and cellular processes dependent on thiamine pyrophosphate (TPP), the active form of thiamine that THTPA helps generate. Methotrexate, aminopterin, and pralatrexate are inhibitors of dihydrofolate reductase (DHFR), an enzyme crucial for folate synthesis. By inhibiting DHFR, these chemicals reduce the production of folate derivatives, consequently decreasing the cellular demand for TPP. The reduced demand for TPP implies a lesser requirement for the enzymatic activity of THTPA, reducing its role within the cell. Similarly, raltitrexed and pemetrexed target thymidylate synthase and other folate-dependent enzymes, leading to a decrease in thymidine monophosphate (TMP), a nucleotide necessary for DNA synthesis that relies on folate cofactors. The inhibition of these pathways by raltitrexed and pemetrexed also suggests a decreased cellular need for TPP, thus lowering the activity of THTPA.
Other inhibitors, such as 5-fluorouracil, yield metabolites like fluorodeoxyuridine monophosphate (FdUMP) that hinder thymidylate synthase, affecting DNA synthesis and, as a result, decreasing the demand for TPP-linked processes. Trimethoprim and pyrimethamine, although primarily focused on bacterial and parasitic DHFR, can be considered as having an indirect effect on human DHFR. This action would similarly suggest a reduced folate pool and, therefore, a lower demand for TPP and THTPA activity. Agents like sulfamethoxazole and triamterene, while not directly targeting folate synthesis enzymes, can lead to diminished folate levels in cells through inhibition of folate uptake or synthesis, which in turn would reduce TPP requirements. Lastly, fluorophenylalanine and cycloguanil, while not directly related to folate metabolism, can also lead to reduced cellular metabolic activity that translates into a decreased necessity for TPP and the catalytic activity of THTPA.
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Items 1 to 10 of 11 total
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Methotrexate | 59-05-2 | sc-3507 sc-3507A | 100 mg 500 mg | $92.00 $209.00 | 33 | |
Methotrexate inhibits dihydrofolate reductase (DHFR), an enzyme involved in tetrahydrofolate synthesis. THTPA phosphorylates thiamine to thiamine pyrophosphate, a cofactor for enzymes in the pentose phosphate pathway, which relies on folate derivatives. Inhibition of DHFR by Methotrexate decreases folate derivatives, potentially reducing THTPA activity due to lower demand for thiamine pyrophosphate in biosynthesis. | ||||||
Fluorouracil | 51-21-8 | sc-29060 sc-29060A | 1 g 5 g | $36.00 $149.00 | 11 | |
5-Fluorouracil is metabolized to fluorodeoxyuridine monophosphate (FdUMP), which inhibits thymidylate synthase, an enzyme that requires folate cofactors for DNA synthesis. As folate derivatives are depleted, the cellular requirement for thiamine pyrophosphate-dependent enzymes, which THTPA helps generate, is reduced, indirectly decreasing THTPA's functional role. | ||||||
Raltitrexed | 112887-68-0 | sc-219933 | 10 mg | $143.00 | ||
Raltitrexed inhibits thymidylate synthase, reducing the synthesis of thymidine monophosphate (TMP), a folate-dependent process. This inhibition could lower the cellular demand for thiamine-dependent processes and indirectly reduce THTPA activity by decreasing the need for its product, thiamine pyrophosphate. | ||||||
Pemetrexed Disodium | 150399-23-8 | sc-219564 | 10 mg | $133.00 | 5 | |
Pemetrexed inhibits multiple folate-dependent enzymes, including DHFR, thymidylate synthase, and glycinamide ribonucleotide formyltransferase. By inhibiting these enzymes, pemetrexed may indirectly decrease the need for thiamine pyrophosphate produced by THTPA, thereby reducing THTPA's activity. | ||||||
Trimethoprim | 738-70-5 | sc-203302 sc-203302A sc-203302B sc-203302C sc-203302D | 5 g 25 g 250 g 1 kg 5 kg | $66.00 $158.00 $204.00 $707.00 $3334.00 | 4 | |
Trimethoprim selectively inhibits bacterial DHFR. Although its primary action is antibacterial, its DHFR inhibition could conceptually extend to an indirect decrease in human DHFR activity, thereby reducing folate production and indirectly decreasing the demand for thiamine pyrophosphate that THTPA generates. | ||||||
Pyrimethamine | 58-14-0 | sc-208190 sc-208190A sc-208190B | 1 g 5 g 25 g | $78.00 $233.00 $809.00 | 5 | |
Pyrimethamine is an inhibitor of DHFR. While it is mainly used as an antimalarial agent, its inhibition of DHFR could lead to a reduced folate pool, thereby indirectly reducing the cellular demand for thiamine pyrophosphate catalyzed by THTPA. | ||||||
L-4-Fluorophenylalanine hydrochloride | 64231-54-5 | sc-235459 sc-235459A | 500 mg 100 mg | $294.00 $104.00 | ||
Fluorophenylalanine acts as a competitive inhibitor for phenylalanine incorporation into proteins. While its primary effect is protein synthesis inhibition, this could lead to reduced metabolic activity and a consequent indirect reduction in thiamine pyrophosphate demand, thereby reducing THTPA activity. | ||||||
Aminopterin | 54-62-6 | sc-202461 | 50 mg | $102.00 | 1 | |
Aminopterin is a potent inhibitor of DHFR. By inhibiting DHFR, it decreases the production of tetrahydrofolate and its derivatives, which may indirectly lead to a reduced requirement for thiamine pyrophosphate and thus lower THTPA activity. | ||||||
Folotyn | 146464-95-1 | sc-364491 sc-364491A | 10 mg 50 mg | $480.00 $1455.00 | ||
Pralatrexate is designed to inhibit DHFR with high affinity. It may reduce the availability of folate cofactors, which are necessary for nucleotide synthesis pathways that also depend on thiamine pyrophosphate. This could indirectly inhibit THTPA by lowering the demand for its product. | ||||||
Sulfamethoxazole | 723-46-6 | sc-208405 sc-208405A sc-208405B sc-208405C | 10 g 25 g 50 g 100 g | $36.00 $54.00 $68.00 $107.00 | 5 | |
Sulfamethoxazole is a sulfonamide antibiotic that inhibits dihydropteroate synthase in bacteria. If this inhibition were to occur in human cells, it could lead to a decrease in folate synthesis, subsequently reducing the requirement for thiamine pyrophosphate and indirectly inhibiting THTPA. | ||||||