RFC Inhibitors
Chemical inhibitors of the Replication Factor C (RFC) exhibit their effects through various mechanisms that impede DNA replication and repair processes. Aphidicolin, a tetracyclic diterpene antibiotic, specifically targets DNA polymerases α and δ, which are critical for DNA synthesis. RFC, which is essential for sliding the PCNA clamp onto DNA, thereby facilitating replication, is functionally hindered due to the inhibition of DNA polymerase δ by Aphidicolin. Similarly, Hydroxyurea limits the availability of deoxyribonucleotide pools by inhibiting ribonucleotide reductase, a key enzyme for DNA synthesis. This reduction in nucleotide availability restricts the activity of RFC, as it requires nucleotides for PCNA clamp loading and subsequent DNA synthesis. On the other hand, Gemcitabine, a nucleoside analog, gets incorporated into DNA, thus disrupting the natural progression of DNA replication where RFC is operative.
Further inhibitory effects on RFC come from agents that induce DNA damage. β-lapachone, a natural quinone, interferes with DNA repair mechanisms, which are contingent upon the functionality of RFC. Topoisomerase inhibitors such as Camptothecin and Etoposide create single-strand and double-strand DNA breaks, respectively. These breaks in the DNA structure render the substrate unsuitable for RFC's action. Likewise, DNA intercalators and cross-linking agents, like Doxorubicin and Mitomycin C, respectively, distort the DNA helix, thereby obstructing the RFC-mediated loading of PCNA. Cisplatin exerts its effect by forming DNA adducts and intrastrand crosslinks, which pose a block to the replication machinery, including RFC. Actinomycin D binds to DNA and inhibits transcriptional elongation, indirectly affecting RFC which is dependent on the proper structure and integrity of DNA for its function. Bleomycin, which cleaves DNA strands through oxidative damage, also indirectly impedes RFC's ability to operate by damaging the very DNA it acts upon. Fludarabine, as a purine analog, disrupts both DNA polymerization and nucleotide synthesis, further impeding the action of RFC in DNA replication.
SEE ALSO...
Items 1 to 10 of 12 total
Display:
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
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 tetracyclic diterpene antibiotic that specifically inhibits DNA polymerase α and δ. RFC is essential for loading the sliding clamp PCNA onto DNA, a process necessary for DNA polymerase δ function, thus Aphidicolin inhibits RFC indirectly by inhibiting DNA polymerase δ. | ||||||
β-Lapachone | 4707-32-8 | sc-200875 sc-200875A | 5 mg 25 mg | $112.00 $459.00 | 8 | |
β-lapachone is a natural quinone compound known to induce topoisomerase I-mediated DNA damage. The RFC complex is required for DNA repair processes, and the inhibition of DNA repair by β-lapachone would render RFC unable to properly function in this pathway. | ||||||
Camptothecin | 7689-03-4 | sc-200871 sc-200871A sc-200871B | 50 mg 250 mg 100 mg | $58.00 $186.00 $94.00 | 21 | |
Camptothecin is a topoisomerase I inhibitor that prevents DNA relegation, leading to single-strand breaks. RFC, involved in DNA replication and repair, requires intact DNA strands to function, thus camptothecin indirectly inhibits RFC by compromising DNA integrity. | ||||||
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 is a chemotherapeutic agent that inhibits DNA topoisomerase II, causing DNA strand breaks. RFC's role in DNA replication and repair is inhibited by etoposide's induction of DNA damage and the resulting inaccessibility of the DNA substrate for RFC. | ||||||
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 is an alkylating agent that cross-links DNA, impeding DNA replication and transcription. Since RFC is involved in DNA replication, the cross-linking of DNA by Mitomycin C would indirectly inhibit the function of RFC by blocking the progression of replication forks. | ||||||
Cisplatin | 15663-27-1 | sc-200896 sc-200896A | 100 mg 500 mg | $138.00 $380.00 | 101 | |
Cisplatin forms DNA adducts and intrastrand crosslinks, thereby disrupting DNA replication. The function of RFC, which is to load PCNA during DNA replication, is indirectly inhibited as the DNA structure is altered, preventing proper clamp loading. | ||||||
Hydroxyurea | 127-07-1 | sc-29061 sc-29061A | 5 g 25 g | $78.00 $260.00 | 18 | |
Hydroxyurea is an inhibitor of ribonucleotide reductase which decreases the deoxyribonucleotide pools required for DNA synthesis. RFC depends on the availability of nucleotides for clamp loading and DNA synthesis, and thus its function is indirectly inhibited by Hydroxyurea. | ||||||
2′-Deoxy-2′,2′-difluorocytidine | 95058-81-4 | sc-275523 sc-275523A | 1 g 5 g | $56.00 $128.00 | ||
Gemcitabine is a nucleoside analog that, once incorporated into DNA, inhibits DNA synthesis. RFC indirectly experiences functional inhibition since the nucleoside analog incorporation into DNA impedes the progression of DNA replication where RFC operates. | ||||||
Actinomycin D | 50-76-0 | sc-200906 sc-200906A sc-200906B sc-200906C sc-200906D | 5 mg 25 mg 100 mg 1 g 10 g | $74.00 $243.00 $731.00 $2572.00 $21848.00 | 53 | |
Actinomycin D binds to DNA at the transcription initiation complex, preventing elongation. Although not directly inhibiting RFC, it compromises the integrity of DNA, thereby preventing RFC from effectively participating in DNA replication and repair. | ||||||
Doxorubicin | 23214-92-8 | sc-280681 sc-280681A | 1 mg 5 mg | $176.00 $426.00 | 43 | |
Doxorubicin intercalates into DNA and inhibits topoisomerase II, creating DNA breaks. As RFC is critical for DNA replication and repair, the DNA damage caused by doxorubicin indirectly inhibits the proper function of RFC. | ||||||