MMR2 Inhibitors
Chemical inhibitors of MMR2 encompass a range of compounds that impede the protein's ability to conduct its vital role in mismatch repair within the cellular environment. Caffeine, as a phosphodiesterase inhibitor, heightens intracellular cAMP, which in turn activates protein kinase A. The activation of this kinase can lead to the phosphorylation of MMR2, a modification that can alter the protein's activity, effectively reducing its ability to correct mismatches in DNA. Similarly, olaparib, by its action as a PARP inhibitor, leads to the accumulation of single-strand DNA breaks. These breaks can divert the DNA repair machinery toward pathways other than mismatch repair, indirectly taxing MMR2 and hindering its corrective function.
Agents such as etoposide and camptothecin target topoisomerases, stabilizing DNA-topoisomerase complexes and preventing the ligation of DNA strands. This results in an accumulation of DNA breaks, which can overwhelm the cellular repair machinery, including MMR2, and indirectly inhibit its function. Methotrexate, through its inhibition of dihydrofolate reductase, leads to a depletion of nucleotide pools, which can result in an increase in DNA mismatches. These mismatches can exceed the repair capacity of MMR2, leading to an indirect inhibition of its activity. Similarly, cisplatin, by forming DNA adducts and cross-links, can sequester the MMR2 protein and exhaust its repair capabilities, while mitomycin C, through the introduction of cross-links between DNA strands, can overwhelm the DNA repair system, diverting it from its normal mismatch repair function. Additionally, aphidicolin and hydroxyurea, by inhibiting DNA polymerases and ribonucleotide reductase respectively, lead to replication stress and a reduction in the substrates required for DNA repair. This can saturate the MMR2 repair capacity and strain its ability to maintain genomic integrity. Finally, 5-fluorouracil, after being metabolized, leads to an increase in uracil incorporation into DNA, which can overwhelm the repair capacity of MMR2, and actinomycin D, by intercalating into DNA, disrupts replication and transcription, which can lead to a multitude of DNA lesions that the MMR2 protein must process, thereby indirectly inhibiting its function.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Caffeine | 58-08-2 | sc-202514 sc-202514A sc-202514B sc-202514C sc-202514D | 50 g 100 g 250 g 1 kg 5 kg | $33.00 $67.00 $97.00 $192.00 $775.00 | 13 | |
Caffeine inhibits phosphodiesterase (PDE), which leads to an increase in intracellular cyclic AMP (cAMP) levels. Elevated cAMP activates protein kinase A (PKA), which can phosphorylate and thereby inhibit MMR2, as phosphorylation can regulate the activity of DNA repair proteins, including those involved in mismatch repair. | ||||||
Olaparib | 763113-22-0 | sc-302017 sc-302017A sc-302017B | 250 mg 500 mg 1 g | $210.00 $305.00 $495.00 | 10 | |
Olaparib is a PARP inhibitor that blocks the repair of single-strand DNA breaks, leading to double-strand breaks which require the homologous recombination repair pathway. MMR2 is indirectly inhibited because the accumulation of unrepaired DNA damages leads to cell cycle arrest and can deplete the cellular resources required for MMR2's repair function. | ||||||
Etoposide (VP-16) | 33419-42-0 | sc-3512B sc-3512 sc-3512A | 10 mg 100 mg 500 mg | $51.00 $231.00 $523.00 | 63 | |
Etoposide stabilizes the DNA-topoisomerase II complex after it has broken the DNA chain for replication, preventing the religation of the DNA strands and thereby causing DNA strand breaks. This can lead to an overload of the DNA repair machinery, including MMR2, indirectly inhibiting its function due to the excessive number of double-strand breaks that MMR2 is not primarily responsible for repairing. | ||||||
Camptothecin | 7689-03-4 | sc-200871 sc-200871A sc-200871B | 50 mg 250 mg 100 mg | $58.00 $186.00 $94.00 | 21 | |
Camptothecin inhibits DNA topoisomerase I, preventing the religation of single-strand breaks. The accumulation of single-strand breaks can indirectly inhibit MMR2 by sequestering the repair machinery away from mismatch repair and overwhelming the cell's ability to maintain genomic integrity, thereby hindering the function of mismatch repair proteins like MMR2. | ||||||
Methotrexate | 59-05-2 | sc-3507 sc-3507A | 100 mg 500 mg | $94.00 $213.00 | 33 | |
Methotrexate is a dihydrofolate reductase inhibitor, which leads to a depletion of nucleotide pools through the inhibition of the folate pathway. Reduced availability of nucleotides can indirectly inhibit MMR2 by causing an increased incidence of mismatches during DNA replication, which can saturate MMR2's repair capacity. | ||||||
Cisplatin | 15663-27-1 | sc-200896 sc-200896A | 100 mg 500 mg | $138.00 $380.00 | 101 | |
Cisplatin forms DNA adducts and cross-links which are recognized and processed by various DNA repair mechanisms. The formation of these adducts can sequester and exhaust the repair capacity of MMR2, indirectly inhibiting its ability to repair mismatches by overwhelming the repair system with platinum-induced lesions. | ||||||
Mitomycin C | 50-07-7 | sc-3514A sc-3514 sc-3514B | 2 mg 5 mg 10 mg | $66.00 $101.00 $143.00 | 85 | |
Mitomycin C forms cross-links between DNA strands that can lead to an overload of the DNA repair system, including MMR2. The extensive DNA damage indirectly inhibits the function of MMR2 by diverting the repair system's attention away from mismatch repair and towards cross-link repair. | ||||||
Aphidicolin | 38966-21-1 | sc-201535 sc-201535A sc-201535B | 1 mg 5 mg 25 mg | $84.00 $306.00 $1104.00 | 30 | |
Aphidicolin is a DNA polymerase inhibitor, particularly for DNA polymerase α and δ. By inhibiting DNA replication, aphidicolin can lead to increased replication stress and potentially increased rates of DNA mismatches. This stress can saturate the repair capacity of MMR2, indirectly inhibiting its function through an overload of replication errors that need to be corrected. | ||||||
Hydroxyurea | 127-07-1 | sc-29061 sc-29061A | 5 g 25 g | $78.00 $260.00 | 18 | |
Hydroxyurea inhibits ribonucleotide reductase, leading to a depletion of the deoxyribonucleotide pools necessary for DNA synthesis and repair. This depletion can indirectly inhibit MMR2 by reducing the available substrates for DNA repair processes, including mismatch repair, thus straining MMR2's function. | ||||||
Fluorouracil | 51-21-8 | sc-29060 sc-29060A | 1 g 5 g | $37.00 $152.00 | 11 | |
5-Fluorouracil is metabolized to fluorodeoxyuridine monophosphate (FdUMP), which inhibits thymidylate synthase, leading to thymineless death and an increase in uracil incorporation into DNA. This misincorporation can saturate MMR2's repair capacity, indirectly inhibiting its function, as MMR2 is responsible for repairing base mismatches like uracil misincorporated in place of thymine. | ||||||