A novel inositol mono-phosphatase inhibitor from Memnoniella echinata. Producing organism, fermentation, isolation, physicochemical and in vitro biological properties.
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.
Lam
Y K
YK
Merck Research Laboratories, Rahway, New Jersey 07065.
Wichmann
C F
CF
Meinz
M S
MS
Guariglia
L
L
Giacobbe
R A
RA
Mochales
S
S
Kong
L
L
Honeycutt
S S
SS
Zink
D
D
Bills
G F
GF
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006168:Guinea Pigs; D003904:Mitosporic Fungi / Q000737:chemistry*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010306:Parotid Gland / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D001572:Benzofurans; D004791:Enzyme Inhibitors; D012717:Sesquiterpenes; D013141:Spiro Compounds; C077631:L 671776; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase