Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C6H8NO8P.2Na |
| Molecular Weight | 299.0829 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[Na+].OC(=O)C[C@H](NC(=O)CP([O-])([O-])=O)C(O)=O
InChI
InChIKey=CZLKTMHQYXYHOO-QTNFYWBSSA-L
InChI=1S/C6H10NO8P.2Na/c8-4(2-16(13,14)15)7-3(6(11)12)1-5(9)10;;/h3H,1-2H2,(H,7,8)(H,9,10)(H,11,12)(H2,13,14,15);;/q;2*+1/p-2/t3-;;/m0../s1
| Molecular Formula | Na |
| Molecular Weight | 22.98976928 |
| Charge | 1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C6H8NO8P |
| Molecular Weight | 253.1034 |
| Charge | -2 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Sparfosate (PALA) is a stable transition state analogue for an aspartate transcarbamylase- cartalyzed reaction with antineoplastic activity. PALA is a potent inhibitor of aspartate transcarbamylase (Ki about 10(-8) M for ACTases of various origins), which in whole cells blocks the de novo synthesis of pyrimidines. Thus PALA inhibits de novo pyrimidine biosynthesis and increases the extent to which fluorouracil metabolites are incorporated into RNA. In vivo, low doses of PALA inhibit whole body pyrimidine synthesis. While this action is cytotoxic in vitro, extensive human testing demonstrates that PALA alone is devoid of selective antitumor activity. Interest in the therapeutic action of PALA derives from the demonstration that its action potentiates the cytotoxicity of several cytotoxic drugs, notably 5-fluorouracil (5-FU). Development of Sparfosate for cancer and Hepatitis B treatment is assumed to have been discontinued.
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.436 mM CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
0.458 mM CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
1000 mg/m² single, intravenous dose: 1000 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1.107 mM CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
1500 mg/m² single, intravenous dose: 1500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
3.68 mM CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
2000 mg/m² single, intravenous dose: 2000 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
33.4 mM × min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
75.55 mM × min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
1000 mg/m² single, intravenous dose: 1000 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
94.7 mM × min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
1500 mg/m² single, intravenous dose: 1500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
247 mM × min CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
2000 mg/m² single, intravenous dose: 2000 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3.72 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
5.25 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
1000 mg/m² single, intravenous dose: 1000 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
5.05 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
1500 mg/m² single, intravenous dose: 1500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
4.08 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/7371023/ |
2000 mg/m² single, intravenous dose: 2000 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
SPARFOSIC ACID plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil based chemotherapy. | 2007-10-15 |
|
| Structural model of the R state of Escherichia coli aspartate transcarbamoylase with substrates bound. | 2007-08-31 |
|
| Continued survival of more than ten years, without resection of metastatic disease, in patients with metastatic colorectal cancer treated with biomodulated fluorouracil: report of two cases. | 2006-03 |
|
| 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. | 2005-12-20 |
|
| Efficient synthesis of fluorothiosparfosic acid analogues with potential antitumoral activity. | 2005-08-15 |
|
| Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with organic phosphates and phosphonates. | 2005-03-15 |
|
| Integrated allosteric regulation in the S. cerevisiae carbamylphosphate synthetase - aspartate transcarbamylase multifunctional protein. | 2004-05-05 |
|
| A fluorescent probe-labeled Escherichia coli aspartate transcarbamoylase that monitors the allosteric conformational state. | 2004-01-09 |
|
| Synthesis and biological evaluation of S-acyl-3-thiopropyl prodrugs of N-phosphonoacetyl-L-aspartate (PALA). | 2003-10 |
|
| Molecular cloning, recombinant expression and partial characterization of the aspartate transcarbamoylase from Toxoplasma gondii. | 2002-02 |
|
| Fluorouracil modulation in colorectal cancer: lack of improvement with N -phosphonoacetyl- l -aspartic acid or oral leucovorin or interferon, but enhanced therapeutic index with weekly 24-hour infusion schedule--an Eastern Cooperative Oncology Group/Cancer and Leukemia Group B Study. | 2001-05-01 |
|
| Sparfosate. A novel biomodulator of 5-fluorouracil. | 2000-02-25 |
|
| The role of low-dose PALA in biochemical modulation. | 1990 |
|
| Phase I trial of combination therapy of cancer with N-phosphonacetyl-L-aspartic acid and dipyridamole. | 1987 |
|
| A comparative study of PALA, PALA plus 5-FU, and 5-FU in advanced breast cancer. | 1985-09-15 |
|
| Clinical trial of sequential N-phosphonacetyl-L-aspartate, thymidine, and 5-fluorouracil in advanced colorectal carcinoma. | 1984-10 |
Sample Use Guides
Colorectal cancer: 250 mg/m2 by rapid IV infusion, given on day 1 with a 24 hour 5-FU IV infusion, 2600 mg/m2, beginning 24 hours later
Route of Administration:
Intravenous
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 17:57:10 GMT 2025
by
admin
on
Mon Mar 31 17:57:10 GMT 2025
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| Record UNII |
5R33Q73DYD
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| Record Status |
Validated (UNII)
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| Record Version |
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NCI_THESAURUS |
C272
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NCI_THESAURUS |
C471
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66569-27-5
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5R33Q73DYD
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300000055231
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DTXSID20985168
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CHEMBL37681
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12908924
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C2353
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| Related Record | Type | Details | ||
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PARENT -> SALT/SOLVATE |
