DPYS Inhibitors
Chemical inhibitors of DPYS can act through various indirect mechanisms to reduce the protein's activity by influencing the availability of its substrates or the balance of nucleotide metabolism. Methotrexate and 5-Fluorouracil, for example, target enzymes involved in the folate cycle and pyrimidine synthesis. Methotrexate inhibits dihydrofolate reductase, disrupting the production of tetrahydrofolate, a necessary cofactor for pyrimidine nucleotide formation. With reduced tetrahydrofolate levels, the substrate availability for DPYS is indirectly diminished. Similarly, 5-Fluorouracil and its metabolite, Fluorodeoxyuridine, inhibit thymidylate synthase, resulting in decreased thymidine levels. The reduction in thymidine constrains the pool of nucleotides upon which DPYS acts, leading to an indirect inhibition of its catabolic function.
Allopurinol and its analog Thiopurinol inhibit xanthine oxidase and, while primarily affecting purine metabolism, lead to an indirect feedback inhibition of DPYS by altering the nucleotide synthesis pathway and increasing pyrimidine synthesis. This increase can result in a feedback mechanism that suppresses DPYS activity. In a similar vein, 6-Mercaptopurine and Azathioprine, through their effects on purine metabolism, can cause fluctuations in the nucleotide pool, which indirectly affect the balance of pyrimidine synthesis and degradation that DPYS is involved in. Reverse transcriptase inhibitors such as Didanosine and Zidovudine indirectly reduce the synthesis of pyrimidine nucleotides, thereby decreasing the substrates available for DPYS. Furthermore, Ribavirin, Mycophenolic acid, and Tiazofurin, by inhibiting enzymes like inosine monophosphate dehydrogenase, disrupt the balance of nucleotide pools. These disruptions indirectly influence DPYS by either depleting substrates needed for its enzymatic processes or by altering the synthesis-degradation equilibrium of pyrimidine nucleotides, thus impacting DPYS's role in nucleotide catabolism.
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Methotrexate | 59-05-2 | sc-3507 sc-3507A | 100 mg 500 mg | $94.00 $213.00 | 33 | |
Methotrexate is a dihydrofolate reductase inhibitor that can lead to reduced production of tetrahydrofolate. Given that DPYS is involved in pyrimidine degradation, a reduction in folate pools can indirectly inhibit the activity of DPYS by limiting the availability of substrates necessary for the production of pyrimidine bases. | ||||||
Fluorouracil | 51-21-8 | sc-29060 sc-29060A | 1 g 5 g | $37.00 $152.00 | 11 | |
5-Fluorouracil is metabolized to fluorodeoxyuridine monophosphate, which inhibits thymidylate synthase, leading to a decrease in thymidine, one of the substrates for pyrimidine biosynthesis. This creates a feedback loop that can inhibit DPYS activity by reducing the concentration of its substrates. | ||||||
Allopurinol | 315-30-0 | sc-207272 | 25 g | $131.00 | ||
Allopurinol is an inhibitor of xanthine oxidase, and while it primarily affects purine metabolism, its action results in the shunting of nucleotide metabolism toward increased pyrimidine synthesis. This indirect effect can result in feedback inhibition of DPYS due to the increased pyrimidine synthesis. | ||||||
6-Mercaptopurine | 50-44-2 | sc-361087 sc-361087A | 50 mg 100 mg | $72.00 $104.00 | ||
6-Mercaptopurine gets incorporated into DNA and RNA and also affects purine metabolism. The resulting increase in pyrimidine synthesis through feedback mechanisms can lead to an indirect inhibition of DPYS by altering the balance of nucleotide synthesis and degradation. | ||||||
Azathioprine | 446-86-6 | sc-210853D sc-210853 sc-210853A sc-210853B sc-210853C | 500 mg 1 g 2 g 5 g 10 g | $203.00 $176.00 $349.00 $505.00 $704.00 | 1 | |
Azathioprine is metabolized into 6-mercaptopurine. It can lead to alterations in purine metabolism and, as a consequence, can indirectly inhibit DPYS by influencing the nucleotide pool and its synthesis-degradation balance. | ||||||
3′-Azido-3′-deoxythymidine | 30516-87-1 | sc-203319 | 10 mg | $61.00 | 2 | |
Zidovudine is another reverse transcriptase inhibitor that can reduce the synthesis of pyrimidine-containing DNA strands. This can indirectly result in a lower substrate availability for DPYS. | ||||||
Ribavirin | 36791-04-5 | sc-203238 sc-203238A sc-203238B | 10 mg 100 mg 5 g | $63.00 $110.00 $214.00 | 1 | |
Ribavirin, a guanosine analog, can inhibit inosine monophosphate dehydrogenase, causing a depletion of the guanosine triphosphate pool and an imbalance in nucleotide pools. This can indirectly inhibit DPYS by perturbing the overall nucleotide metabolism. | ||||||
Mycophenolic acid | 24280-93-1 | sc-200110 sc-200110A | 100 mg 500 mg | $69.00 $266.00 | 8 | |
Mycophenolic acid is an inhibitor of inosine monophosphate dehydrogenase which leads to decreased guanine nucleotides and thereby impacts the overall nucleotide synthesis and degradation balance. This can indirectly inhibit DPYS by reducing its substrate availability. | ||||||
Tiazofurin | 60084-10-8 | sc-475805 | 5 mg | $449.00 | ||
Tiazofurin inhibits inosine monophosphate dehydrogenase, leading to reduced levels of NAD+ and alterations in the nucleotide synthesis. These changes can indirectly inhibit DPYS by affecting the levels of pyrimidine nucleotides required for its enzymatic activity. | ||||||