MedKoo product information:

PN401

PN-401 is a synthetic uridine pro-drug that is converted to uridine in vivo. Uridine, a pyrimidine nucleotide, has been used in a variety of diseases including depressive disorders and inherited myopathies. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

PN401, an oral prodrug of uridine yields more bioavailable uridine than oral administration of uridine itself. PN401 may therefore be useful for permitting dose escalation of 5-fluorouracil (5-FU) with consequent improvements in antitumor efficacy.   PN401 was shown to be protective in the mitochondrial complex II inhibitor 3-nitropropionic acid model of Huntington's disease (HD). Research results suggest that PN401 may have beneficial effects in the treatment of neurodegenerative diseases such as HD. see Neurobiol Dis. 2006 Dec;24(3):455-65.

Current developer:     Wellstat Therapeutics Corporation

 1. Saydoff, Joel A.; Garcia, Rolando A. G.; Browne, Susan E.; Liu, Liansheng; Sheng, Jin; Brenneman, Denise; Hu, Zhongyi; Cardin, Sylvain; Gonzalez, Alexis; von Borstel, Reid W.; Gregorio, Jason; Burr, Holly; Beal, M. Flint. Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse models of Huntington's disease. Neurobiology of Disease (2006), 24(3), 455-465. CODEN: NUDIEM ISSN:0969-9961. CAN 146:266494 AN 2006:1245538

2. Doroshow, James H.; McCoy, Sheryl; Macdonald, John S.; Issell, Brian F.; Patel, Taral; Cobb, Patrick W.; Yost, Kathleen J.; Abbruzzese, James L. Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: A Southwest Oncology Group study. Investigational New Drugs (2006), 24(6), 537-542. CODEN: INNDDK ISSN:0167-6997. CAN 146:414364 AN 2006:834313

3. Saif, Muhammad Wasif; Borstel, Reid. 5-Fluorouracil dose escalation enabled with PN401 (triacetyluridine): toxicity reduction and increased antitumor activity in mice. Cancer Chemotherapy and Pharmacology (2006), 58(1), 136-142. CODEN: CCPHDZ ISSN:0344-5704. CAN 145:327796 AN 2006:375032

4. Garcia, Rolando A. G.; Liu, Liansheng; Hu, Zhongyi; Gonzalez, Alexis; von Borstel, Reid W.; Saydoff, Joel A. Severe cytochrome c oxidase inhibition in vivo does not induce a pyrimidine deficiency; neuroprotective action of oral uridine prodrug PN401 requires supraphysiological levels of uridine. Brain Research (2005), 1066(1-2), 164-171. CODEN: BRREAP ISSN:0006-8993. CAN 144:81045 AN 2005:1319808

5. Saydoff, J.; Liu, L.; Hu, Z.; von Borstel, R. Uridine prodrug PN401 is beneficial in APP2576 mice and models for chemical hypoxia and oxidative stress. Vascular Dementia, International Congress, 3rd, Prague, Czech Republic, Oct. 23-26, 2003 (2003), 241-245. CODEN: 69GVAS CAN 143:71599 AN 2005:397109

6. Saydoff, Joel A.; Liu, Lian Sheng; Garcia, Rolando A. G.; Hu, Zhongyi; Li, Donna; von Borstel, Reid W. Oral uridine pro-drug PN401 decreases neurodegeneration, behavioral impairment, weight loss and mortality in the 3-nitropropionic acid mitochondrial toxin model of Huntington's disease. Brain Research (2003), 994(1), 44-54. CODEN: BRREAP ISSN:0006-8993. CAN 140:174995 AN 2003:923611

7. Hidalgo, Manuel; Villalona-Calero, Miguel A.; Eckhardt, S. Gail; Drengler, Ronald L.; Rodriguez, Gladys; Hammond, Lisa A.; Diab, Sami G.; Weiss, Geoffrey; Garner, Allison M.; Campbell, Elizabeth; Davidson, Karen; Louie, Arthur; O'Neil, James D.; Von Borstel, Reid; Von Hoff, Daniel D.; Rowinsky, Eric K. Phase I and pharmacologic study of PN401 and fluorouracil in patients with advanced solid malignancies. Journal of Clinical Oncology (2000), 18(1), 167-177. CODEN: JCONDN ISSN:0732-183X. CAN 132:102547 AN 2000:61094

8. Kelsen, David P.; Martin, Dan; O'neil, James; Schwartz, Gary; Saltz, Leonard; Sung, Michael T.; Von Borstel, Reid; Bertino, Joseph. Phase I trial of PN401, an oral prodrug of uridine, to prevent toxicity from fluorouracil in patients with advanced cancer. Journal of Clinical Oncology (1997), 15(4), 1511-1517. CODEN: JCONDN ISSN:0732-183X. CAN 126:325035 AN 1997:283216