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Chemical Compound Review

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

Synonyms: USNUS-08, Sparfosic acid, CHEMBL504802, NCIMech_000444, NSC-224131, ...
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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


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  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]
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  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]
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  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]
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  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]
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  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]
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