Sparfosic acid

Sparfosic acid is a DNA antimetabolite agent and a potent inhibitor of aspartate transcarbamoyl transferase. Sparfosic acid has anti-tumor activity. Aspartate transcarbamoyl transferase catalyzes the second step of de novo pyrimidine biosynthesis[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Metabolic Disease

Sparfosic acid (PALA) causes apoptosis in the resistant Br1 cells[1]. Sparfosic acid (300 µM) shows progressive accumulation of cells in S phase and activation of an apoptotic pathway leading to cell death[1]. Cell Viability Assay[1] Cell Line: Br-l and L-2 cell lines established from metastasis in nude mouse injected with the human tumor cell line MDA-MB-435 Concentration: 300 µM Incubation Time: 12, 24 and 48 hours Result: Cells were predominantly in S phase in both the cell lines, although slightly higher proportion of cells in S phase were noted in L-2 than Brl-3prl cells. Western Blot Analysis[1] Cell Line: Br-l and L-2 cell lines Concentration: 300 µM Incubation Time: 4, 10 and 24 hours Result: There was moderate difference in the level of phosphorylated Rb proteins seen in the two cell types.Marked increase in the amount of cyclin A protein was detected in the L-2 cells undergoing apoptosis with the highest level detected at 10 h post-drug treatment.In contrast, there was no increase in the level of cyclin A seen in the Brl-3prl cells.Cyclin E protein was found elevated in the L-2 cells and Brl-3prl cells compared to their respective controls.

[1]. Wang J, et al. Elevated cyclin A associated kinase activity promotes sensitivity of metastatic human cancer cells to DNA antimetabolite drug. Int J Oncol. 2015 Aug;47(2):782-90.

[2]. Angela D. Morris, et al. A New, Efficient, Two Step Procedure for the Preparation of the Antineoplastic Agent Sparfosic Acid.

MOLECULAR FORMULA :

C6-H10-N-O8-P

MOLECULAR WEIGHT :

255.14

WISWESSER LINE NOTATION :

QV1YVQMV1PQQO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human

DOSE/DURATION :

862 mg/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

5 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

5 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system

MUTATION DATA

TEST SYSTEM :

Mammal - dog

DOSE/DURATION :

20 mg/kg

REFERENCE :

CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 43,2565,1983