Cephalon, Inc.

E.i. Dupont De Nemours and Company

The Medical College of Wisconsin, Inc.

Ernest Knight, Jr

Robert L Hudkins

Michael W Hunkapiller

Bruce D Korant

David J Ganfield

James L Diebold

Matthew S Miller

Lisa D Aimone

Ernest C Borden

Forrest A Haun

Thomas M Engber

Michael Recht

Diana Fahey

Michael S Saporito

Disclosed herein are therapeutic methologies utilizing a ring substituted derivative of the indolocarbazole K-252a, the derivative represented by the formula:

Use of K-252a derivative

Disclosed in this patent document are synthetic, biologically active molecules referred to as fused pyrrolo�2,3-c!carbazole-6-ones. These molecules are represented by the following general formulae: ##STR1## Methods for making and using the fused pyrrolo�2,3-c!carbazole-6-ones are also disclosed.

Fused pyrrolo�2,3-C! carbazole-6-ones

Disclosed herein are compounds referred to as 'fused pyrrolocarbazoles' which possess a variety of functional pharmacological activities including effect on the function and/or survival of trophic factor responsive cells; inhibition of enzymatic activity; inhibition of inflammation-associated responses; inhibition of cell growth associated with hyperproliferative states; and inhibition of developmentally programmed motoneuron death. The disclosed compounds are represented by the following general formula: ##STR1## Methodologies for the synthetic production of fused pyrrolocarbazoles are also disclosed, as well as exemplary uses of the compounds.

Fused pyrrolocarbazoles

Disclosed in this patent document are synthetic, biologically active molecules referred to as fused pyrrolo[2,3-c]carbazole-6-ones. These molecules are represented by the following general formulae: ##STR1## Methods for making and using the fused pyrrolo[2,3-c]carbazole-6-ones are also disclosed.

Fused pyrrolo[2,3-c]carbazole-6-ones

Disclosed herein are compounds referred to as 'fused pyrrolocarbazoles' which possess a variety of functional activities. The disclosed compounds are represented by the following general formula: ##STR1## Methodologies for the synthetic production of fused pyrrolocarbazoles are also disclosed, as well as exemplary, uses of the compounds.

Disclosed herein are compounds referred to as 'fused pyrrolocarbazoles' which possess a variety of functional activities. The disclosed compounds are represented by the following general formula: ##STR1## Methodologies for the synthetic production of fused pyrrolocarbazoles are also disclosed, as well as exemplary uses of the compounds.

Fused Pyrrolocarbazoles

An in vitro method for the production of interferon is set forth. The method involves the culture of monocytes with a new DA15 peptide produced in Daudi cell lines in response to stimulation with interferon gamma.

Production of IFN using DA15 peptide

A protein fraction isolated from tissue cultures of human diploid fibroblasts or lymphoblastoid cells inhibits the growth of heterologous human cells.

Preparation of a protein fraction exhibiting cell growth-inhibiting

Antibodies to the twenty-one acid peptide: (X-Ser-Tyr-Asn-Leu-Leu-Gly-Phe-Leu-Gln-Arg-Ser-Ser-Asn-Phe-Gln-Y-Gln-Lys-L eu-Leu).sub.n, where X is Met or Ser, Y is His or Cys and n is 1 to 12; peptide/protein conjugates and antibodies thereto; process for producing the antibodies; and processes for assaying human fibroblast interferon and for purifying it.

Antibodies to immunogenic peptides and their use to purify human

The twenty-one amino acid peptides, (X-Ser-Tyr-Asn-Leu-Leu-Gly-Phe-Leu-Gln-Arg-Ser-Ser-Asn-Phe-Gln-Y-Gln-Lys-L eu-Leu).sub.n, where X is Met or Ser, Y is His or Cys and n is 1 to 12, useful for assaying human fibroblast interferon and for purifying it.

Immunogenic interferon peptides

Human interferons produced in the absence of added serum or sera can be purified to greater than 95% protein purity by adsorption on immobilized Cibacron Blue F3G-A and eluting the interferon adsorbed on the Cibacron Blue F3G-A with ethylene glycol in an aqueous buffer solution. The purified interferon in solution can be converted to interferon of uniform molecular weight by heating the interferon solution in the presence of an organic thiol compound.

Growing community of inventors

Wilmington, DE, United States of America

Ernest Knight, Jr