The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
Chemical Compound Review

PALA     (2S)-2-(2- phosphonoethanoylamino) butanedio...

Synonyms: USNUS-08, Sparfosic acid, CHEMBL504802, NCIMech_000444, NSC-224131, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of Sparfosic acid

 

High impact information on Sparfosic acid

  • Under the same dissociating conditions, incubating the altered CAD with the ATCase substrate carbamoyl phosphate or the bisubstrate analogue N-phosphonacetyl-L-aspartate unexpectedly leads to the reformation of hexamers [6].
  • Rodent cells resistant to N-phosphonacetyl-L-aspartate (PALA) invariably contain amplified carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase (CAD) genes, usually in widely spaced tandem arrays present as extensions of the same chromosome arm that carries a single copy of CAD in normal cells [7].
  • Multiple mechanisms of N-phosphonacetyl-L-aspartate resistance in human cell lines: carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase gene amplification is frequent only when chromosome 2 is rearranged [7].
  • However, this conclusion derives from studies employing the UMP synthesis inhibitor N-phosphonacetyl-L-aspartate (PALA), which, in addition to selecting for cells containing extra copies of the CAD locus, enables p53-deficient cells to enter S phase and acquire the DNA breaks that initiate the amplification process [8].
  • DNA synthesis also initiates within this OBR in autonomously replicating extrachromosomal amplicons (CAD episomes) located in an N-phosphonacetyl-L-aspartate-resistant clone (5P20) of CHOK1 cells [9].
 

Chemical compound and disease context of Sparfosic acid

 

Biological context of Sparfosic acid

 

Anatomical context of Sparfosic acid

 

Associations of Sparfosic acid with other chemical compounds

 

Gene context of Sparfosic acid

 

Analytical, diagnostic and therapeutic context of Sparfosic acid

References

  1. Response of psoriasis to N-phosphonacetyl-L-aspartate. Earhart, R.H., DeConti, R.C., Rubin, J., Ohnuma, T. Lancet (1981) [Pubmed]
  2. Mechanism of resistance of variants of the Lewis lung carcinoma to N-(phosphonacetyl)-L-aspartic acid. Kensler, T.W., Mutter, G., Hankerson, J.G., Reck, L.J., Harley, C., Han, N., Ardalan, B., Cysyk, R.L., Johnson, R.K., Jayaram, H.N., Cooney, D.A. Cancer Res. (1981) [Pubmed]
  3. Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma. Morton, R.F., Creagan, E.T., Cullinan, S.A., Mailliard, J.A., Ebbert, L., Veeder, M.H., Chang, M. J. Clin. Oncol. (1987) [Pubmed]
  4. Collateral sensitivity to N-(phosphonacetyl)-L-aspartic acid in a line of P388 leukemia cells selected for resistance to L-(alpha S, 5S)-alpha-amino-3- chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin). Ardalan, B., Jayaram, H.N., Johnson, R.K. Cancer Res. (1983) [Pubmed]
  5. Improved therapeutic index with sequential N-phosphonacetyl-L-aspartate plus high-dose methotrexate plus high-dose 5-fluorouracil and appropriate rescue. Martin, D.S., Stolfi, R.L., Sawyer, R.C., Spiegelman, S., Young, C.W. Cancer Res. (1983) [Pubmed]
  6. Substitutions in the aspartate transcarbamoylase domain of hamster CAD disrupt oligomeric structure. Qiu, Y., Davidson, J.N. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. Multiple mechanisms of N-phosphonacetyl-L-aspartate resistance in human cell lines: carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase gene amplification is frequent only when chromosome 2 is rearranged. Smith, K.A., Chernova, O.B., Groves, R.P., Stark, M.B., Martínez, J.L., Davidson, J.N., Trent, J.M., Patterson, T.E., Agarwal, A., Duncan, P., Agarwal, M.L., Stark, G.R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. Gene amplification in a p53-deficient cell line requires cell cycle progression under conditions that generate DNA breakage. Paulson, T.G., Almasan, A., Brody, L.L., Wahl, G.M. Mol. Cell. Biol. (1998) [Pubmed]
  9. Identification of an origin of bidirectional DNA replication in the ubiquitously expressed mammalian CAD gene. Kelly, R.E., DeRose, M.L., Draper, B.W., Wahl, G.M. Mol. Cell. Biol. (1995) [Pubmed]
  10. A single amino acid substitution in the active site of Escherichia coli aspartate transcarbamoylase prevents the allosteric transition. Stieglitz, K.A., Pastra-Landis, S.C., Xia, J., Tsuruta, H., Kantrowitz, E.R. J. Mol. Biol. (2005) [Pubmed]
  11. Mechanism-based model for tumor drug resistance. Kuczek, T., Chan, T.C. Cancer Chemother. Pharmacol. (1992) [Pubmed]
  12. A phase II trial of biochemical modulation using N-phosphonacetyl-L-aspartate, high-dose methotrexate, high-dose 5-fluorouracil, and leucovorin in patients with adenocarcinoma of unknown primary site. Kelsen, D., Martin, D.S., Colofiore, J., Sawyer, R., Coit, D. Cancer (1992) [Pubmed]
  13. In vitro cytotoxic effect of N-(phosphonacetyl)-L-aspartic acid in liposome against C-26 murine colon carcinoma. Kim, J.S., Heath, T.D. Arch. Pharm. Res. (2000) [Pubmed]
  14. Half of Saccharomyces cerevisiae carbamoyl phosphate synthetase produces and channels carbamoyl phosphate to the fused aspartate transcarbamoylase domain. Serre, V., Guy, H., Penverne, B., Lux, M., Rotgeri, A., Evans, D., Hervé, G. J. Biol. Chem. (1999) [Pubmed]
  15. Aspartate transcarbamylase from the hyperthermophilic archaeon Pyrococcus abyssi: thermostability and 1.8A resolution crystal structure of the catalytic subunit complexed with the bisubstrate analogue N-phosphonacetyl-L-aspartate. Van Boxstael, S., Cunin, R., Khan, S., Maes, D. J. Mol. Biol. (2003) [Pubmed]
  16. Embryotoxicity in mice of phosphonacetyl-L-aspartic acid (PALA), a new antitumor agent. I. Embryolethal, teratogenic, and cytogenetic effects. Sieber, S.M., Botkin, C.C., Soong, P., Lee, E.C., Whang-Peng, J. Teratology (1980) [Pubmed]
  17. Peripheral leukocytes as indicators of the enzymatic effects of N-(phosphonacetyl)-L-aspartic acid (PALA) on human L-aspartate transcarbamoylase (ATCase) activity. Kensler, T.W., Erlichman, C., Jayaram, H.N., Tyagi, A.K., Ardalan, B., Cooney, D.A. Cancer treatment reports. (1980) [Pubmed]
  18. Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of this enzyme in the regulation of the pyrimidine salvage pathway and in the activation of fluoropyrimidines. Cao, D., Russell, R.L., Zhang, D., Leffert, J.J., Pizzorno, G. Cancer Res. (2002) [Pubmed]
  19. Effect of N-(phosphonacetyl)-L-aspartate on 5-azacytidine metabolism in P388 and L1210 cells. Grant, S., Rauscher, F., Jakubowski, A., Cadman, E. Cancer Res. (1981) [Pubmed]
  20. The presence of amplified regions affects the stability of chromosomes in drug-resistant Chinese hamster cells. Miele, M., Bonatti, S., Menichini, P., Ottaggio, L., Abbondandolo, A. Mutat. Res. (1989) [Pubmed]
  21. Increased methotrexate resistance and dhfr gene amplification as a consequence of induced Ha-ras expression in NIH 3T3 cells. Wani, M.A., Xu, X., Stambrook, P.J. Cancer Res. (1994) [Pubmed]
  22. Embryotoxicity in mice of phosphonacetyl-L-aspartic acid (PALA), a new antitumor agent. II. Studies on its mechanism and reversibility. Sieber, S.M., Botkin, C.C., Leslie, K.A., Cooney, D.A. Teratology (1980) [Pubmed]
  23. Gas chromatography and mass spectrometry of N-(phosphonacetyl)-L-aspartic acid. Branfman, A.R., Valia, K.H., Bruni, R.J. J. Chromatogr. (1978) [Pubmed]
  24. Determination of N-(phosphonacetyl)-L-aspartic acid (PALA) in plasma and urine by high pressure liquid chromatography. Lankelma, J., Penders, P.G., Leyva, A., Pinedo, H.M. European journal of cancer. (1980) [Pubmed]
 
WikiGenes - Universities