CP 73850

Names

[ Name ]:
CP 73850

[Synonym ]:
2-[4-oxo-3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]phthalazin-1-yl]acetic acid

Biological Activity

[Description]:

Zopolrestat (CP73850) is a potent, orally active aldose reductase (AR) inhibitor with an IC50 of 3.1 nM. Zopolrestat is used for the research of diabetic complications[1].

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Aldose Reductase

Research Areas >> Metabolic Disease

[In Vitro]

Zopolrestat is a potent inhibitor of the reduction of both glyceraldehyde and glucose by the human and rat enzymes[1].

[In Vivo]

Zopolrestat (2.5 mg/kg-50 mg/kg; p.o.; once-a-day for 5 days) and left untreated for 7 days) prevents accumulation of sorbitol in the kidney cortex of diabetic rats and normalize elevated renal blood flow in galactosemic rats[1]. Animal Model: Male Sprague-Dawley rats (made diabetic by iv injection of streptozotocin)[1]. Dosage: 2.5 mg/kg-50 mg/kg Administration: P.o.; once-a-day for 5 days Result: Its ED50s in reversing already elevated sorbitol accumulation in rat sciatic nerve, retina, and lens in a chronic test were 1.9, 17.6, and 18.4 mg/kg, respectively.

[References]

[1]. Mylari BL, et al. Novel, potent aldose reductase inhibitors: 3,4-dihydro-4-oxo-3-[[5-(trifluoromethyl)-2-benzothiazolyl] methyl]-1-phthalazineacetic acid (zopolrestat) and congeners. J Med Chem. 1991;34(1):108-122.

Chemical & Physical Properties

[ Density]:
1.58g/cm3

[ Boiling Point ]:
598.7ºC at 760mmHg

[ Molecular Formula ]:
C₁₉H₁₂F₃N₃O₃S

[ Molecular Weight ]:
419.37700

[ Flash Point ]:
315.9ºC

[ Exact Mass ]:
419.05500

[ PSA ]:
113.32000

[ LogP ]:
3.70040

[ Vapour Pressure ]:
3.5E-15mmHg at 25°C

[ Index of Refraction ]:
1.683

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H413

[ Precautionary Statements ]:
P301 + P310

[ Hazard Codes ]:
T+

[ RIDADR ]:
UN 2811 6.1 / PGIII

Articles

Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase upregulated in cancers.

Eur. J. Pharmacol. 584 , 213-221, (2008)

AKR1B10 is an aldose reductase (AR) homologue overexpressed in liver cancer and various forms of that enzyme in carcinomas catalyze the reduction of anticancer drugs, potential cytostatic drug, and dl...

Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals in mouse peritoneal macrophages.

Cytokine 36(3-4) , 115-22, (2006)

Aldose reductase (AR; AKR1B1) a member of aldo-keto reductase super family, that we had shown earlier mediates cytotoxic signals induced by high glucose, cytokines and growth factors, also mediates th...

Endotoxin causes pulmonary hypertension by upregulating smooth muscle endothelin type-B receptors: role of aldose reductase.

Shock 30(2) , 189-96, (2008)

Endothelin-1 (ET-1), a potent vasoconstrictor and mitogen, is upregulated in pulmonary tissue during endotoxemia and contributes markedly to endotoxin-induced pulmonary hypertension. It is, however, u...