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Details

Stereochemistry ABSOLUTE
Molecular Formula C6H10NO8P
Molecular Weight 255.1193
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SPARFOSIC ACID

SMILES

OC(=O)C[C@H](NC(=O)CP(O)(O)=O)C(O)=O

InChI

InChIKey=ZZKNRXZVGOYGJT-VKHMYHEASA-N
InChI=1S/C6H10NO8P/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)/t3-/m0/s1

HIDE SMILES / InChI

Description

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

PubMed

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
Sparfosate (PALA) is a potent inhibitor of aspartate transcarbamylase (Ki about 10(-8) M for ACTases of various origins)