|Crystallographic structure of ranpirnase in complex with RNA.|
Ranpirnase is a ribonuclease enzyme found in the oocytes of the Northern Leopard Frog (Rana pipiens). Ranpirnase is a member of the pancreatic ribonuclease (RNase A) protein superfamily and degrades RNA substrates with a sequence preference for uracil and guanine nucleotides. Along with amphinase, another leopard frog ribonuclease, ranpirnase has been studied as a potential cancer treatment due to its unusual mechanism of cytotoxicity tested against tumor cells.
Ranpirnase was originally discovered by scientists at TamirBio, a biotechnology company (formerly Alfacell Corporation), where it was tested in clinical trials under the brand name Onconase. The mechanism of action of ranpirnase tumor-selective cytotoxicity has been attributed to the RNA interference pathway, potentially through cleaving siRNA molecules; to cleavage of transfer RNA; and to interference with the NF-κB pathway. Despite early indications of promise as a mesothelioma treatment, and an orphan drug status designation from the United States Food and Drug Administration in 2007, the Phase III clinical trial for this indication did not demonstrate statistical significance against primary endpoints.
- Lee, J. E.; Bae, E; Bingman, C. A.; Phillips Jr, G. N.; Raines, R. T. (2008). "Structural basis for catalysis by onconase". Journal of Molecular Biology 375 (1): 165–77. doi:10.1016/j.jmb.2007.09.089. PMC 2151974. PMID 18001769.
- Ardelt, W; Shogen, K; Darzynkiewicz, Z (2008). "Onconase and amphinase, the antitumor ribonucleases from Rana pipiens oocytes". Current pharmaceutical biotechnology 9 (3): 215–25. PMC 2586917. PMID 18673287.
- Zhao, H; Ardelt, B; Ardelt, W; Shogen, K; Darzynkiewicz, Z (2008). "The cytotoxic ribonuclease onconase targets RNA interference (siRNA)". Cell cycle (Georgetown, Tex.) 7 (20): 3258–61. PMC 2586937. PMID 18927512.
- Nasu, M; Carbone, M; Gaudino, G; Ly, B. H.; Bertino, P; Shimizu, D; Morris, P; Pass, H. I.; Yang, H (2011). "Ranpirnase Interferes with NF-κB Pathway and MMP9 Activity, Inhibiting Malignant Mesothelioma Cell Invasiveness and Xenograft Growth". Genes & Cancer 2 (5): 576–84. doi:10.1177/1947601911412375. PMC 3161417. PMID 21901170.
- Costanzi, J; Sidransky, D; Navon, A; Goldsweig, H (2005). "Ribonucleases as a novel pro-apoptotic anticancer strategy: Review of the preclinical and clinical data for ranpirnase". Cancer Investigation 23 (7): 643–50. doi:10.1080/07357900500283143. PMID 16305992.
- Mikulski, S. M.; Costanzi, J. J.; Vogelzang, N. J.; McCachren, S; Taub, R. N.; Chun, H; Mittelman, A; Panella, T; Puccio, C; Fine, R; Shogen, K (2002). "Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma". Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20 (1): 274–81. PMID 11773179.
- Vogelzang, N. J.; Rusthoven, J. J.; Symanowski, J; Denham, C; Kaukel, E; Ruffie, P; Gatzemeier, U; Boyer, M; Emri, S; Manegold, C; Niyikiza, C; Paoletti, P (2003). "Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma". Journal of Clinical Oncology 21 (14): 2636–44. doi:10.1200/JCO.2003.11.136. PMID 12860938.
- Waknine, Yael. "New FDA Orphan Drugs: Gestiva, Onconase, Aerosolized Ciprofloxacin". Medscape. Retrieved 2 February 2015.
- "Alfacell Annual Report 2009". Retrieved 2 February 2015.
|This enzyme-related article is a stub. You can help Wikipedia by expanding it.|