hMSH3 Inhibitors
Chemical inhibitors of hMSH3 employ various mechanisms to impede its function in DNA mismatch repair. O6-Benzylguanine targets DNA repair pathways by inhibiting AGT, which normally mitigates DNA alkylation damage. When AGT is inhibited, the persistence of alkylation damage can affect hMSH3's repair functions, as hMSH3 is integral in the mismatch repair pathway. Similarly, Trifluoperazine disrupts hMSH3's activities by acting as a calmodulin antagonist, which leads to the inhibition of calcium/calmodulin-dependent protein kinases, potentially altering the phosphorylation state of hMSH3 and its associated repair activities. Chloroquine, with its ability to intercalate into DNA, creates obstacles for hMSH3's interaction with DNA, potentially hindering its ability to recognize and bind to mismatches.
Mitomycin C and cisplatin generate extensive DNA damage through crosslinking, forming adducts that are challenging for the DNA repair machinery to process. Such lesions can saturate hMSH3's capacity, leading to its functional inhibition. Etoposide and camptothecin, by inhibiting topoisomerases, increase DNA breaks and stabilize topoisomerase-DNA complexes, respectively, which can overload hMSH3's repair capabilities. Methotrexate indirectly impacts hMSH3 by reducing the production of thymidylate, a nucleotide essential for DNA synthesis and repair, thus affecting hMSH3's ability to participate in the repair process. Cadmium chloride's interaction with proteins can impact those with zinc-finger motifs, which are crucial for DNA repair activities. If hMSH3 relies on such motifs, its function could be compromised by cadmium. Aflatoxin B1 forms adducts, especially with guanine bases, leading to excessive engagement of hMSH3 with these lesions, which may overwhelm the mismatch repair system. Lastly, Doxorubicin interferes with topoisomerase II, which can block hMSH3's access to DNA mismatches and inhibit its role in DNA error correction.
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Trifluoperazine Dihydrochloride | 440-17-5 | sc-201498 sc-201498A | 1 g 5 g | $56.00 $99.00 | 9 | |
Trifluoperazine, a calmodulin antagonist, can inhibit the calcium/calmodulin-dependent protein kinases (CaMKs). Since hMSH3's stability and function in the MMR pathway can be influenced by phosphorylation events, which may be mediated by kinases like CaMKs, trifluoperazine can disrupt the phosphorylation state of hMSH3, leading to its functional inhibition. | ||||||
Chloroquine | 54-05-7 | sc-507304 | 250 mg | $68.00 | 2 | |
Chloroquine is known to intercalate into DNA, which can affect DNA replication and repair processes. Since hMSH3 is a DNA mismatch repair protein that recognizes and binds to mismatches, the intercalation by chloroquine can hinder the ability of hMSH3 to recognize and bind to its target DNA sequences, thereby inhibiting its function. | ||||||
Mitomycin C | 50-07-7 | sc-3514A sc-3514 sc-3514B | 2 mg 5 mg 10 mg | $65.00 $99.00 $140.00 | 85 | |
Mitomycin C is a DNA crosslinking agent that forms adducts with DNA, thereby impeding DNA replication and repair. The crosslinked DNA is a substrate for the mismatch repair system, and the presence of extensive crosslinking can overwhelm the repair capacity, including the function of hMSH3, leading to its functional inhibition. | ||||||
Etoposide (VP-16) | 33419-42-0 | sc-3512B sc-3512 sc-3512A | 10 mg 100 mg 500 mg | $32.00 $170.00 $385.00 | 63 | |
Etoposide induces DNA breaks by inhibiting the enzyme topoisomerase II. hMSH3 is part of the MMR pathway, which is also involved in the response to DNA breaks. The elevated DNA damage caused by etoposide can saturate the repair capacity of hMSH3, resulting in the functional inhibition of its activity. | ||||||
Cisplatin | 15663-27-1 | sc-200896 sc-200896A | 100 mg 500 mg | $76.00 $216.00 | 101 | |
Cisplatin forms DNA adducts and intrastrand crosslinks that are recognized and processed by the MMR system. The binding of hMSH3 to these lesions without subsequent repair can lead to futile repair cycles, depleting cellular resources and inhibiting the normal function of hMSH3. | ||||||
Methotrexate | 59-05-2 | sc-3507 sc-3507A | 100 mg 500 mg | $92.00 $209.00 | 33 | |
Methotrexate is a dihydrofolate reductase inhibitor that leads to a decrease in the production of thymidylate, an essential precursor for DNA synthesis and repair. By limiting the availability of thymidylate, methotrexate indirectly hampers the DNA replication and repair processes in which hMSH3 is involved, thus inhibiting its function. | ||||||
Cadmium chloride, anhydrous | 10108-64-2 | sc-252533 sc-252533A sc-252533B | 10 g 50 g 500 g | $55.00 $179.00 $345.00 | 1 | |
Cadmium chloride can disrupt DNA repair mechanisms by binding to proteins and displacing zinc ions from zinc-finger motifs, which are important for protein-DNA interactions. If hMSH3 requires such zinc-finger motifs for its activity, cadmium can inhibit its DNA-binding capability and thus its function in DNA repair. | ||||||
Camptothecin | 7689-03-4 | sc-200871 sc-200871A sc-200871B | 50 mg 250 mg 100 mg | $57.00 $182.00 $92.00 | 21 | |
Camptothecin is a topoisomerase I inhibitor that prevents the religation of DNA strands after topoisomerase I-induced single-strand breaks. The resulting stabilized topoisomerase I-DNA cleavable complexes can block the access of MMR proteins, including hMSH3, to the DNA, thereby inhibiting its function. | ||||||
Doxorubicin | 23214-92-8 | sc-280681 sc-280681A | 1 mg 5 mg | $173.00 $418.00 | 43 | |
Doxorubicin intercalates into DNA and disrupts topoisomerase II-mediated DNA repair. This intercalation can hinder the MMR process by blocking the access of hMSH3 to DNA mismatches, thereby inhibiting its function in the recognition and repair of DNA errors. | ||||||