Ranpirnase(Redirected from Onconase)
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 preclinical assays and in clinical trials under the name Pannon or Onconase, respectively. 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. Currently (as of May 2017) Ranpirnase is in Phase I clinical study for treatment of anogenital warts.
- Lee JE, Bae E, Bingman CA, Phillips GN, Raines RT (January 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 (June 2008). "Onconase and amphinase, the antitumor ribonucleases from Rana pipiens oocytes". Current Pharmaceutical Biotechnology. 9 (3): 215–25. doi:10.2174/138920108784567245. PMC 2586917. PMID 18673287.
- Darzynkiewicz Z, Carter SP, Mikulski SM, Ardelt WJ, Shogen K. Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent.Cell Tissue Kinet. 1988 May;21(3):169-82. PMID 3224365
- Zhao H, Ardelt B, Ardelt W, Shogen K, Darzynkiewicz Z (October 2008). "The cytotoxic ribonuclease onconase targets RNA interference (siRNA)". Cell Cycle. 7 (20): 3258–61. doi:10.4161/cc.7.20.6855. PMC 2586937. PMID 18927512.
- Nasu M, Carbone M, Gaudino G, Ly BH, Bertino P, Shimizu D, Morris P, Pass HI, Yang H (May 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 SM, Costanzi JJ, Vogelzang NJ, McCachren S, Taub RN, Chun H, Mittelman A, Panella T, Puccio C, Fine R, Shogen K (January 2002). "Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma". Journal of Clinical Oncology. 20 (1): 274–81. doi:10.1200/JCO.2002.20.1.274. PMID 11773179.
- Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C, Paoletti P (July 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" (PDF). Retrieved 2 February 2015.
- Squiquera L, Taxman DJ, Brendle SA, Torres R, Sulley J, Hodge T, Christensen N, Sidransky D. Ranpirnase eradicates human papillomavirus in cultured cells and heals anogenital warts in a Phase I study. Antivir Ther. 2017 Jan 25. doi: 10.3851/IMP3133. PMID 28121292.
|This enzyme-related article is a stub. You can help Wikipedia by expanding it.|