Rad18 Activators
RAD18 Activators are a diverse group of chemical compounds that, through indirect mechanisms, enhance the functional activity of RAD18, a key protein in DNA damage tolerance and post-replication repair. In the cellular landscape, RAD18's activity is modulated by various DNA damage response (DDR) pathways. Compounds like Caffeine, VE 821, AZD6738, and ATR Inhibitor (AZ20) play a crucial role in this modulation. These compounds, primarily by inhibiting ATR kinase, reduce the phosphorylation-dependent inactivation of RAD18, thereby facilitating RAD18's role in response to replication stress and DNA damage. This is particularly significant in the context of maintaining genomic stability during DNA replication. Similarly, Olaparib and Veliparib, both PARP inhibitors, contribute to RAD18 activation by increasing the prevalence of single-strand breaks and replication fork stalling. These DNA lesions necessitate RAD18-mediated repair mechanisms, such as translesion synthesis, highlighting RAD18's importance in the cellular response to DNA damage.
Further emphasizing the interconnectedness of DDR pathways and RAD18's role, compounds like NU 7441, ATM Kinase Inhibitor, and MRN-ATM Pathway Inhibitor, Mirin target other key proteins in DDR. NU 7441 and ATM Kinase Inhibitor, by inhibiting DNA-PKcs and ATM kinases respectively, disrupt conventional DNA repair pathways (like non-homologous end joining), increasing the reliance on RAD18-mediated repair mechanisms. MRN-ATM Pathway Inhibitor, Mirin, targeting MRE11, affects the MRN complex's role in DNA repair, again shifting the cellular dependency towards RAD18-mediated pathways. Additionally, the WEE1 Inhibitor (2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1,2-dihydropyrazolo[3,4-d]pyrimidin-3-one) and Chk1 Inhibitor (PF 477736) contribute to RAD18's activation by exacerbating replication stress, thereby enhancing the necessity for RAD18's involvement in DNA repair and tolerance mechanisms. The CHK2 Inhibitor (BML-277) further illustrates this principle by modulating the response to DNA damage and replication stress, augmenting the reliance on RAD18. Collectively, these RAD18 Activators, through their targeted inhibition of various DDR kinases and pathways, underscore the critical role of RAD18 in ensuring genomic integrity and highlight the intricate network of cellular responses to DNA damage.
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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, a known inhibitor of ATM and ATR kinases, indirectly enhances RAD18 activity. By inhibiting ATM/ATR, caffeine reduces the phosphorylation-dependent inactivation of RAD18, thus facilitating its role in post-replication repair and DNA damage tolerance pathways. | ||||||
Olaparib | 763113-22-0 | sc-302017 sc-302017A sc-302017B | 250 mg 500 mg 1 g | $210.00 $305.00 $495.00 | 10 | |
Olaparib, a PARP inhibitor, indirectly enhances RAD18 function. Inhibition of PARP leads to persistent single-strand breaks which, if unrepaired, can collapse replication forks and necessitate RAD18-mediated post-replication repair and translesion synthesis, thus indirectly promoting RAD18's DNA repair activity. | ||||||
NU 7441 | 503468-95-9 | sc-208107 | 5 mg | $357.00 | 10 | |
NU 7441, a DNA-PKcs inhibitor, can indirectly increase RAD18 activity. By inhibiting DNA-PKcs, it disrupts non-homologous end joining, potentially increasing reliance on alternative DNA repair mechanisms like those mediated by RAD18, thereby enhancing RAD18's role in DNA damage tolerance and repair. | ||||||
MRN-ATM Pathway Inhibitor, Mirin | 299953-00-7 | sc-203144 | 10 mg | $141.00 | 4 | |
Mirin, an MRE11 inhibitor, indirectly enhances RAD18 activity. By inhibiting MRE11, mirin disrupts the MRN complex's role in DNA damage sensing and repair, potentially increasing the need for RAD18-mediated post-replication repair mechanisms in the context of replication stress and DNA damage. | ||||||
Ceralasertib | 1352226-88-0 | sc-507439 | 10 mg | $573.00 | ||
AZD6738, an ATR inhibitor, indirectly promotes RAD18 activity. Similar to VE-821, it reduces ATR-mediated phosphorylation of RAD18, thus supporting RAD18's role in the cellular response to replication stress and post-replication repair processes. | ||||||
2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1,2-dihydropyrazolo[3,4-d]pyrimidin-3-one | 955365-80-7 | sc-483196 | 5 mg | $340.00 | 1 | |
2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1,2-dihydropyrazolo[3,4-d]pyrimidin-3-one, a WEE1 kinase inhibitor, indirectly enhances RAD18 activity. By inhibiting WEE1, it leads to unscheduled entry into mitosis and replication stress, which in turn necessitates RAD18-mediated DNA damage tolerance mechanisms, thereby indirectly promoting RAD18's role in DNA repair. | ||||||
PF 477736 | 952021-60-2 | sc-362781 sc-362781A | 5 mg 25 mg | $115.00 $431.00 | ||
PF 477736, a Chk1 inhibitor, indirectly augments RAD18 activity. Inhibition of Chk1 exacerbates replication stress and DNA damage, leading to an increased dependency on RAD18-mediated post-replication repair pathways for maintaining genomic stability. | ||||||
Veliparib | 912444-00-9 | sc-394457A sc-394457 sc-394457B | 5 mg 10 mg 50 mg | $182.00 $275.00 $726.00 | 3 | |
Veliparib, a PARP inhibitor like Olaparib, indirectly enhances RAD18 activity. It increases the occurrence of single-strand breaks and replication fork stalling, which in turn elevates the need for RAD18-mediated repair pathways, particularly in the context of translesion synthesis and post-replication repair. | ||||||
AZ20 | 1233339-22-4 | sc-503186 | 5 mg | $255.00 | 1 | |
AZ20, an ATR inhibitor, indirectly enhances RAD18 activity. It operates similarly to VE-821 and AZD6738 by reducing ATR-mediated phosphorylation of RAD18, thus supporting RAD18's function in response to replication stress and DNA damage, particularly in post-replication repair processes. | ||||||
BML-277 | 516480-79-8 | sc-200700 sc-200700A | 10 mg 50 mg | $132.00 $492.00 | 2 | |
BML-277, a CHK2 inhibitor, indirectly enhances RAD18 activity. By inhibiting CHK2, it modulates the cellular response to DNA damage and replication stress, potentially increasing the reliance on RAD18-mediated DNA repair pathways for maintaining genomic stability and cell survival. | ||||||