You can buy Nuparp at the lowest price at Nextgen.ooo online pharmacy. Rucaparib is a potent inhibitor of mammalian poly(ADP-ribose) polymerase (PARP) 1, 2, and 3 with antitumor properties. PPAR is an enzyme that plays an important role in DNA repair by activating response pathways and facilitating repair, and defects in these repair mechanisms have been demonstrated in a variety of malignancies, including cancer. Regulation of repair pathways is critical to ensuring proper cell death. BRCA genes are tumor suppressor genes that mediate several cellular processes, including DNA replication, transcriptional regulation, cell cycle checkpoints, apoptosis, chromatin structuring, and homologous recombination (HR). Homologous recombination deficiency (HRD), along with PPAR inhibition, is a vulnerability that enhances the cell death pathway when mutations alone provide viability. Ovarian cancer typically has defects in DNA repair pathways such as HRD, due to BRCA mutations or other causes.
 
Rupaparib was granted accelerated approval in 2016 for use as oral monotherapy in patients with a BRCA mutation (germline and/or somatic) associated with advanced ovarian cancer for select patients who have received more than two prior lines of platinum-based therapy. Identification of patients eligible for rucaparib is accomplished using in vitro diagnostic tests to detect the presence of a deleterious BRCA mutation (germline and/or somatic). The FDA-approved test qualitatively detects sequence changes in the BRCA1 and BRCA2 (BRCA1/2) genes.
 
While rucaparib is indicated for the treatment of advanced BRCA mutation-associated ovarian cancer (germline and/or somatic), there is evidence that its antitumor activity is also clinically effective against ovarian tumors with high homologous recombination deficiency (HRD) and loss of heterozygosity (LOH).
 
Poly(ADP-ribose) polymerase (PARP) enzymes play a role in DNA repair. PPAR-1 is responsible for the repair of single-strand breaks (SSBs) in base excision repair (BER). PARP1 is also involved in the regulation of non-homologous end joining (NHEJ), chromatin remodeling, and homologous recombination (HR) DNA repair pathways. When PARP is inhibited, single-strand breaks become double-strand breaks, which are usually repaired by homologous recombination. Pre-existing homologous recombination deficiency (HRD) may arise from mutations in the BRCA1 or BRCA2 genes, which allows for persistent repair and growth of cancer cells.
 
Rucaparib is an inhibitor of PARP-1, PARP-2, and PARP-3. By inhibiting PARP enzymatic activity, rucaparib reduces the formation of PARP-DNA complexes that lead to DNA damage, apoptosis, and cell death markers. PARP inhibition is thought to specifically target tumor cells with pre-existing HRD, such as cells harboring mutations in the BRCA1 or BRCA2 genes. Rucaparib induces synthetic lethality by disrupting single- and double-strand repair pathways that lead to tumor cell death. It is also thought that PARP inhibition may result in PARP-1 entrapment of damaged DNA, effectively preventing further DNA repair; defective recruitment of BRCA1 to damaged DNA; and activation of alternative DNA repair such as error-prone non-homologous end joining (NHEJ) or alternative end joining pathways leading to mutations or chromosomal changes and ultimately cell death.