Description |
L-Canavanine sulfate is a selective inhibitor of inducible NO synthase.
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Target |
NO synthase[1]
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In Vitro |
L-Canavanine sulfate (L-CAV) causes only a limited degree of cytotoxicity in HeLa, Hep G2, and SK-HEP-1 cells when given alone in arginine-rich media with IC50 values ranging from 5 to 10 mM. In HaCaT keratinocyte cell line, IC50 of L-Canavanine sulfate exceeds the concentration of 10 mM, indicating low cytotoxicity in normal cells in vitro. In arginine-free media, IC50 of L-Canavanine sulfate in HeLa, Hep G2, and SK-HEP-1 cells are 0.21±0.04; 0.64±0.16; and 1.18±0.14 mM, respectively. L-Canavanine sulfate, which is hardly toxic alone, potentiates the cytotoxicity of vinblastine (VIN) and paclitaxel (PTX) in HeLa and hepatocellular carcinoma cells[2].
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In Vivo |
Administration of L-Canavanine sulfate (100 mg/kg) produces a moderate increase in mean arterial pressure of 20 mm Hg, returns blood pressure to near basal levels and completely attenuates the lipopolysaccharide-induced hypotension. All, but one, endotoxaemic rats dosed with L-Canavanine sulfate (100 mg/kg) survive for 6 h post lipopolysaccharide, after which time the experiment is terminated (n=7)[1]. L-canavanine inhibits DNA synthesis by Li 210 cells in vivo and significantly increases the lifespan of animals bearing the Li 210 leukemia. An optimal dose of 18 g/kg produces a peak increase in lifespan of 44%. The therapeutic dose range is narrow, and a dose of 24 g/kg causes death due to drug toxicity[3].
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Cell Assay |
A dose-dependent cytotoxicity is examined using the MTT assay. Into each well of 96-well plates, 2×104 of cells are seeded, and after 24 h incubation, cells are incubated with test compounds (including L-Canavanine sulfate). After 24 h, 0.5 mg/mL of MTT is added to each well of HeLa, Caco-2, MIA PaCa-2, BxPC-3 and SK-HEP-1 cells, while MTT is added to Hep G2 after 48 h incubation with test compounds (including L-Canavanine sulfate). The cells are then incubated for 3 h so that the viable cells could produce formazan crystals; they are then dissolved in 100 μL DMSO. After incubation for 10 min in a shaker, the absorption of the formazan is measured at 570 nm using a reader[2].
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Animal Admin |
Male rats weighing 295 to 305 g are used. After a period of stabilization, 6 mg lipopolysaccharide/kg is administered intravenously in 0.3 mL over 2 min, and cardiovascular parameters are monitored over 5 to 6 h. L-Canavanine sulfate is administered intravenously in a 0.2 mL volume bolus injection at 100 mg/kg[1]. Mice: L-Canavanine is dissolved in phosphate-buffered saline[1]. L-Canavanine (100 mg/mb) is infused at a rate of 0.1 mL/hr through a catheter implanted S.C. over the back. Groups of 5 mice are treated at each dose beveltogether with 6 to 8 control animals and are inspected twice per day for median time of death[1].
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Boiling Point | 574ºC at 760mmHg |
Flash Point | 300.9ºC |
Exact Mass | 274.058319 |
PSA | 217.43000 |
LogP | 0.52230 |
Vapour Pressure | 1.21E-08mmHg at 25°C |
Storage condition | 2-8°C |