The University of Texas System

Alnylam Pharmaceuticals, Inc.

Other

Genentech, Inc.

Merck + Co., Inc.

Michael S Brown

Joseph L Goldstein

Yuval Reiss

David W Russell

Pamela Tan

Juergen Soutschek

Thomas C Sudhof

Jay D Horton

Young-Ah Moon

Xiaodong Wang

Guy L James

Michael R Briggs

Jing Yang

Robert S McDowell

David A Oare

Mark E Reynolds

Todd C Somers

Thomas E Rawson

Craig W Crowley

James C Marsters

Jin Ye

Patrcik G Harran

Tong-Jin Zhao

Chunfu Wang

Dong Cheng

Juan Carlos Jaen

Leping Li

David W Martin, Jr

Nick V Grishin

Michael J Gale

Michael Gale, Jr

Rhea Sumpter, Jr

Peter J Espenshade

Robert B Rawson

Juro Sakai

Jim Marsters

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a SCAP gene (Human SCAP gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of a SCAP gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Human SCAP expression and the expression of a SCAP gene using the pharmaceutical composition; and methods for inhibiting the expression of a SCAP gene in a cell.

RNAi modulation of SCAP and therapeutic uses thereof

Ghrelin O-acyltransferase (GOAT) is inhibited with designed small molecules of the general formula: Methods comprise contacting the GOAT with an inhibitor and detecting a resultant inhibition.

Small molecule inhibitors of ghrelin O-acyltransferase

Ghrelin O-acyltransferase (GOAT) is inhibited with designed small molecules. Methods comprise contacting the GOAT with an inhibitor and detecting a resultant inhibition.

Disclosed are methods and compositions for the identification of inhibitors of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme. The most potent inhibitors are ones in which phenylalanine occurs at the third position of a tetrapeptide whose amino terminus is cysteine.

Method for identifying farnesyl transferase inhibitors

RNAi modulation of SCAP and therapeutics uses thereof

Ghrelin is acylated by ghrelin O-acyltransferase. Ghrelin O-acyltransferase assays comprise contacting a mixture of ghrelin and recombinant ghrelin O-acyltransferase with an agent; and detecting a resultant decrease in acylation of the ghrelin by the acyltransferase.

Ghrelin o-acyltransferase (GOAT) biochemical assay

Permissiveness of human cells to replication of susceptible pathogenic human viruses is reduced by treating the cells with a selective inhibitor of prenylation of a host cell protein. Target viruses, especially Flaviviridae, are predetermined to lack a CXXX box and prenylated viral protein, and to be replication-dependent on host protein prenylation. The general method comprises (a) contacting human cells subject to infection by the virus with an effective amount of a selective inhibitor of a prenylation enzyme of the cells; and (b) confirming a resultant reduction in permissiveness of the cells to replication of the virus. Targeted enzymes include prenyl biosynthetic enzyme like HMG CoA reductase farnesyl and/or geranylgeranyl transferase enzymes.

Prenylation inhibitors reduce host cell permissiveness to viral replication

Agents that modulate an interaction of an FBL2 protein with an NS5A or NS5B Flaviviridae protein in a mixture are identified by contacting the mixture with a candidate agent under conditions wherein but for the presence of the agent, the FBL2 protein and the Flaviviridae protein engage in a reference interaction; and detecting an agent-biased interaction. Flaviviridae replication is inhibited by contacting a Flaviviridae-infected cell with an FBL2-specific reagent; and detecting a resultant Flaviviridae replication inhibition.

FBL2-specific agents as modulators of Flaviviridae RNA replication

An apparatus, which can be secured to a vehicle, and which can be used to affix, transport, and deploy shooting sports equipment such as a target dispenser, or a gun-sighting bench rest assembly. The apparatus is most commonly secured to and transported by an all-terrain vehicle.

Transportable shooting apparatus

Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme. The most potent inhibitors are ones in which phenylalanine occurs at the third position of a tetrapeptide whose amino terminus is cysteine.

Methods and compositions for inhibiting farnesyl transferase enzyme

Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21 . One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21 . Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme. The most potent inhibitors are ones in which phenylalanine occurs at the third position of a tetrapeptide whose amino terminus is cysteine.

Method of inhibiting a farnesyl transferase enzyme

Compounds, compositions and methods are provided for the inhibition of S1 protease and for the modulation of cholesterol homeostasis in a cell.

Modulators of SREBP processing

Methods of assaying farnesyl transferase

Growing community of inventors

Dallas, TX, United States of America

Michael S Brown