Merck + Co., Inc.

Kevin M Byrne

Louis Kaplan

Sheo B Singh

Anne W Dombrowski

John G Ondeyka

Dan A Ostlind

Joyce A Greene

Diane M Vesey

Arlene M Dahl

Deborah L Zink

Shieh-Shung T Chen

Byron H Arison

Otto D Hensens

Jerrold M Liesch

Robert T Goegelman

Raymond F White

Linda S Wicker

Brian R Petuch

Mary N Omstead

John G MacConnell

Jennifer Nielsen Kahn

Robert P Borris

Richard J Monaghan

Novel compounds isolated from the fermentation of producing cultures of Nodulisporium sp. are antiparasitic and insecticidal agents.

Antiparasitic agents

Described is a new immunosuppressant, L-687,819, a C-31 demethylated derivative of L-683,795 (FK-523), produced under fermentation conditions utilizing the new mutant microorganism, Streptomyces hygroscopicus subsp. ascomyceticus (Merck Culture Collection MA 6646) ATCC No. 53855, being a blocked mutant of Streptomyces hygroscopicus subsp. ascomyceticus (MA 6475) ATCC No. 14891. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Microbial immunoregulant

Disclosed are new Aspergillus niger mutants which can be used for identifying active FK-506/ rapamycin type, or cyclosporin A type inununosuppressants in a broth, natural product extract, or composition exhibiting inununosuppressant activity. Specifically disclosed are the new mutants, ATCC No. 74085 (MF 5659), which is sensitive to FK-506 and rapamycin but resistant to cyclosporin A; ATCC No. 74086 (MF 5659) which is resistant to FK-506, cyclosporin A and rapamycin; and ATCC No. 74087 (MF 5661) which is resistant to FK-506 and rapamycin, but sensitive to cyclosporin A.

Aspergillus niger mutants

Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthetase inhibitors and thus useful as cholesterol lowering agents, antifungal agents and cancer treatment agents.

Cholesterol lowering compounds produced by directed biosynthesis

Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthetase inhibitors useful as cholesterol-lowering agents.

Directed biosynthesis of cholesterol lowering compounds

Disclosed is a novel lipophilic macrolide of Formula I: ##STR1## The compound of assigned Formula I is an analog of rapamycin which has activity as an antifungal agent and as an immunosuppressant.

Lipophilic macrolide useful as an immunosuppressant

Growing community of inventors

West Trenton, NJ, United States of America

Kevin M Byrne