Fugger, Kasper; Bajrami, Ilirjana; Silva Dos Santos, Mariana; Young, Sarah Jane; Kunzelmann, Simone; Kelly, Geoff; Hewitt, Graeme; Patel, Harshil; Goldstone, Robert; Carell, Thomas; Boulton, Simon J.; MacRae, James; Taylor, Ian A.; West, Stephen C. published an article in 2021, the title of the article was Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors.Product Details of 4433-40-3 And the article contains the following content:
Mutations in the BRCA1 or BRCA2 tumor suppressor genes predispose individuals to breast and ovarian cancer. In the clinic, these cancers are treated with inhibitors that target poly(ADP-ribose) polymerase (PARP). We show that inhibition of DNPH1, a protein that eliminates cytotoxic nucleotide 5-hydroxymethyl-deoxyuridine (hmdU) monophosphate, potentiates the sensitivity of BRCA-deficient cells to PARP inhibitors (PARPi). Synthetic lethality was mediated by the action of SMUG1 glycosylase on genomic hmdU, leading to PARP trapping, replication fork collapse, DNA break formation, and apoptosis. BRCA1-deficient cells that acquired resistance to PARPi were resensitized by treatment with hmdU and DNPH1 inhibition. Because genomic hmdU is a key determinant of PARPi sensitivity, targeting DNPH1 provides a promising strategy for the hypersensitization of BRCA-deficient cancers to PARPi therapy. The experimental process involved the reaction of 5-(Hydroxymethyl)pyrimidine-2,4(1H,3H)-dione(cas: 4433-40-3).Product Details of 4433-40-3
The Article related to dnph1 brca parp inhibitor sensitizer nucleotide sanitizer smug1, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Product Details of 4433-40-3
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia