Abstract
A novel inositol mono-phosphatase inhibitor, L-671,776 (1), was discovered from a culture of the hyphomycete, Memnoniella echinata (ATCC 20928). 1 has a molecular weight of 388 and a molecular formula of C23H32O5. The mode of inhibition is non-competitive, with a Ki of 450 microM. It shows no inhibition of myo-inositol 1,4-bisphosphate 1-phosphatase or myo-inositol 1,4,5-triphosphate 5-phosphatase, although it weakly inhibits myo-inositol 1,4,5-triphosphate 3-kinase (IC50 = 3 mM). It elevates inositol monophosphates in rat parotid slices (EC50 approximately 3 mM), but abolishes agonist effects. It also produces short-lived contraction of guinea pig trachea at 300 microM.
MeSH terms
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Animals
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Benzofurans / chemistry
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Benzofurans / isolation & purification*
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Benzofurans / pharmacology
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification*
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Enzyme Inhibitors / pharmacology
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Guinea Pigs
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Mitosporic Fungi / chemistry*
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Parotid Gland / drug effects
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Phosphoric Monoester Hydrolases / antagonists & inhibitors*
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Phosphoric Monoester Hydrolases / metabolism
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Rats
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Sesquiterpenes / chemistry
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Sesquiterpenes / isolation & purification*
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Sesquiterpenes / pharmacology
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Spiro Compounds / chemistry
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Spiro Compounds / isolation & purification*
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Spiro Compounds / pharmacology
Substances
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Benzofurans
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Enzyme Inhibitors
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Sesquiterpenes
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Spiro Compounds
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L 671776
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Phosphoric Monoester Hydrolases
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myo-inositol-1 (or 4)-monophosphatase