CA2076652A1 - Methods and compositions for the identification, characterization and inhibition of farnesyl protein transferase - Google Patents

Methods and compositions for the identification, characterization and inhibition of farnesyl protein transferase

Info

Publication number
CA2076652A1
CA2076652A1 CA002076652A CA2076652A CA2076652A1 CA 2076652 A1 CA2076652 A1 CA 2076652A1 CA 002076652 A CA002076652 A CA 002076652A CA 2076652 A CA2076652 A CA 2076652A CA 2076652 A1 CA2076652 A1 CA 2076652A1
Authority
CA
Canada
Prior art keywords
enzyme
disclosed
inhibition
identification
methods
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002076652A
Other languages
French (fr)
Other versions
CA2076652C (en
Inventor
Michael S. Brown
Joseph L. Goldstein
Yuval Reiss
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
Original Assignee
Michael S. Brown
Joseph L. Goldstein
Yuval Reiss
Board Of Regents, The University Of Texas System
The Board Of Regents Of The University Of Texas
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27056998&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2076652(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Michael S. Brown, Joseph L. Goldstein, Yuval Reiss, Board Of Regents, The University Of Texas System, The Board Of Regents Of The University Of Texas filed Critical Michael S. Brown
Publication of CA2076652A1 publication Critical patent/CA2076652A1/en
Application granted granted Critical
Publication of CA2076652C publication Critical patent/CA2076652C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/82—Translation products from oncogenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1019—Tetrapeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/02—Linear peptides containing at least one abnormal peptide link
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1085—Transferases (2.) transferring alkyl or aryl groups other than methyl groups (2.5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00—Chemistry: molecular biology and microbiology
    • Y10S435/814—Enzyme separation or purification
    • Y10S435/815—Enzyme separation or purification by sorption

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Analytical Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transfer-ases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 up-on 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 p21ras. Also disclosed is a family 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.
CA002076652A 1990-04-18 1991-04-18 Methods and compositions for the identification, characterization and inhibition of farnesyl protein transferase Expired - Lifetime CA2076652C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US51070690A 1990-04-18 1990-04-18
US510,706 1990-04-18
US615,715 1990-11-20
US07/615,715 US5141851A (en) 1990-04-18 1990-11-20 Isolated farnesyl protein transferase enzyme
PCT/US1991/002650 WO1991016340A1 (en) 1990-04-18 1991-04-18 Methods and compositions for the identification, characterization and inhibition of farnesyl protein transferase

Publications (2)

Publication Number Publication Date
CA2076652A1 true CA2076652A1 (en) 1991-10-19
CA2076652C CA2076652C (en) 2003-06-10

Family

ID=27056998

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002076652A Expired - Lifetime CA2076652C (en) 1990-04-18 1991-04-18 Methods and compositions for the identification, characterization and inhibition of farnesyl protein transferase

Country Status (8)

Country Link
US (1) US5141851A (en)
EP (1) EP0528820B2 (en)
JP (1) JPH05506779A (en)
AT (1) ATE143973T1 (en)
AU (1) AU637497B2 (en)
CA (1) CA2076652C (en)
DE (2) DE69122611T3 (en)
WO (1) WO1991016340A1 (en)

Families Citing this family (126)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5976851A (en) * 1990-04-18 1999-11-02 Board Of Regents, The University Of Texas System Methods and compositions for the identification, characterization, and inhibition of farnesyl protein transferase
US6083917A (en) * 1990-04-18 2000-07-04 Board Of Regents, The University Of Texas System Methods and compositions for the identification, characterization and inhibition of farnesyltransferase
US6790633B1 (en) * 1990-04-18 2004-09-14 Michael S. Brown Method of inhibiting a farnesyl transferase enzyme
US8003342B1 (en) 1990-04-18 2011-08-23 Board Of Regents, The University Of Texas System Method for identifying farnesyl transferase inhibitors
US5420245A (en) * 1990-04-18 1995-05-30 Board Of Regents, The University Of Texas Tetrapeptide-based inhibitors of farnesyl transferase
US5962243A (en) * 1990-04-18 1999-10-05 Board Of Regents, The University Of Texas System Methods for the identification of farnesyltransferase inhibitors
US6632626B1 (en) * 1990-04-18 2003-10-14 Board Of Regents, The University Of Texas System Methods of assaying farnesyl transferase
US5185248A (en) * 1990-05-08 1993-02-09 E. R. Squibb & Sons, Inc. Farnesyl-protein transferase assay for identifying compounds that block neoplastic transformation
CA2044333A1 (en) * 1990-06-12 1991-12-13 Jackson B. Gibbs Chemotherapeutic agents
US5776892A (en) * 1990-12-21 1998-07-07 Curative Health Services, Inc. Anti-inflammatory peptides
CA2072033A1 (en) * 1991-06-28 1992-12-29 Jackson B. Gibbs Non-substrate inhibitors of farnesyl protein transferase
EP0528486A2 (en) * 1991-08-16 1993-02-24 Merck & Co. Inc. Non-substrate inhibitors of farnesyl protein transferase
US5298655A (en) * 1991-09-27 1994-03-29 Merck & Co., Inc. Farnesyl pyrophosphate analogs
US5340828A (en) * 1991-09-30 1994-08-23 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5238922A (en) * 1991-09-30 1993-08-24 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5366871A (en) * 1991-11-13 1994-11-22 The University Of Utah Ubiquitin-peptide extensions as enzyme substrates
US5420157A (en) * 1991-12-16 1995-05-30 Merck & Co., Inc. Inhibitors of farnesyl protein transferase or prodrugs thereof
US5260465A (en) * 1991-12-16 1993-11-09 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5260479A (en) * 1991-12-16 1993-11-09 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5245061A (en) * 1991-12-16 1993-09-14 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
GB2267966A (en) * 1992-06-17 1993-12-22 Merck & Co Inc A fluorescence assay for farnesyl protein transferase activity
US5352705A (en) * 1992-06-26 1994-10-04 Merck & Co., Inc. Inhibitors of farnesyl protein transferase
US5326773A (en) * 1992-10-29 1994-07-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5536750A (en) * 1992-10-29 1996-07-16 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5504212A (en) * 1992-10-29 1996-04-02 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5686472A (en) * 1992-10-29 1997-11-11 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5821118A (en) * 1992-10-30 1998-10-13 Merck & Co., Inc. Genes for the subunits of human farnesyl-protein transferase
US5578477A (en) * 1993-01-05 1996-11-26 Arch Development Corporation Identification and characterization of inhibtors of protein farnesyltransferase
EP0621342A1 (en) * 1993-04-20 1994-10-26 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Reagent and kit for determining isoprenylating activity and inhibition thereof
US5952473A (en) * 1993-04-20 1999-09-14 Cohen; Louis Hartog Reagent and kit for determining isoprenylating activity and inhibition thereof
EP0763537A3 (en) * 1993-05-14 1997-10-22 Genentech Inc Non-peptidyl Ras farnesyl transferase inhibitors
US5965539A (en) * 1993-05-18 1999-10-12 Univeristy Of Pittsburgh Inhibitors of prenyl transferases
US5705686A (en) * 1993-05-18 1998-01-06 University Of Pittsburgh Inhibition of farnesyl transferase
US6011175A (en) * 1993-05-18 2000-01-04 University Of Pittsburgh Inhibition of farnesyltransferase
US5602098A (en) * 1993-05-18 1997-02-11 University Of Pittsburgh Inhibition of farnesyltransferase
US5834434A (en) * 1993-05-18 1998-11-10 University Of Pittsburgh Inhibitors of farnesyltransferase
JPH09500109A (en) * 1993-06-18 1997-01-07 メルク エンド カンパニー インコーポレーテッド Inhibitors of farnesyl protein transferase
CA2172125A1 (en) * 1993-09-30 1995-04-06 S. Jane Desolms Inhibitors of farnesyl-protein transferase
US5719148A (en) * 1993-10-15 1998-02-17 Schering Corporation Tricyclic amide and urea compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5661152A (en) * 1993-10-15 1997-08-26 Schering Corporation Tricyclic sulfonamide compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US6365588B1 (en) 1993-10-15 2002-04-02 Schering Corporation Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US6075025A (en) 1993-10-15 2000-06-13 Schering Corporation Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5721236A (en) * 1993-10-15 1998-02-24 Schering Corporation Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5763577A (en) * 1993-10-25 1998-06-09 Warner-Lambert Company Substituted tetra- and pentapeptide inhibitors of protein: farnesyl transferase
US5439918A (en) 1994-03-14 1995-08-08 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
JP3969737B2 (en) * 1994-03-15 2007-09-05 エーザイ株式会社 Isoprenyl transferase inhibitor
US5436263A (en) * 1994-03-22 1995-07-25 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5420334A (en) * 1994-04-04 1995-05-30 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5523430A (en) * 1994-04-14 1996-06-04 Bristol-Myers Squibb Company Protein farnesyl transferase inhibitors
CA2190846A1 (en) * 1994-05-20 1995-11-30 John S. Wai Inhibitors of farnesyl-protein transferase
US5510371A (en) * 1994-06-06 1996-04-23 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5571792A (en) * 1994-06-30 1996-11-05 Warner-Lambert Company Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase
US5576313A (en) * 1994-08-29 1996-11-19 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5830868A (en) * 1994-09-13 1998-11-03 Warner-Lambert Company Substituted DI- and tripeptide inhibitors of protein: farnesyl transferase
IT1273986B (en) * 1994-09-28 1997-07-14 Merck & Co Inc PEPTIDAL INHIBITORS OF FARNESIL PROTEIN TRANSFERASE
WO1996010034A2 (en) * 1994-09-29 1996-04-04 Merck & Co., Inc. Thiol-free inhibitors of farnesyl-protein transferase
US5491164A (en) * 1994-09-29 1996-02-13 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5585359A (en) * 1994-09-29 1996-12-17 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5652257A (en) * 1994-09-29 1997-07-29 Merck & Co., Inc. Heterocycle-containing inhibitors of farnesyl-protein transferase
US5523456A (en) * 1994-09-29 1996-06-04 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5661161A (en) * 1994-09-29 1997-08-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5571835A (en) * 1994-09-29 1996-11-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5574025A (en) * 1994-10-26 1996-11-12 Merck & Co., Inc. Inhibitors of prenyl-protein transferases
FR2730492B1 (en) * 1995-02-09 1997-03-14 Rhone Poulenc Rorer Sa NOVEL FARNESYL TRANSFERASE INHIBITORS, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
FR2730491B1 (en) * 1995-02-09 1997-03-14 Rhone Poulenc Rorer Sa NOVEL FARNESYL TRANSFERASE INHIBITORS, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US5684013A (en) * 1995-03-24 1997-11-04 Schering Corporation Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5700806A (en) * 1995-03-24 1997-12-23 Schering Corporation Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5624936A (en) * 1995-03-29 1997-04-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5578629A (en) * 1995-03-29 1996-11-26 Merck & Co., Inc. Benzamide-containing inhibitors of farnesyl-protein transferase
US5631280A (en) * 1995-03-29 1997-05-20 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5856326A (en) * 1995-03-29 1999-01-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5627202A (en) * 1995-03-29 1997-05-06 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5534537A (en) * 1995-03-29 1996-07-09 Merck & Co., Inc. Prodrugs of inhibitors of farnesyl-protein transferase
US5801175A (en) 1995-04-07 1998-09-01 Schering Corporation Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5891872A (en) * 1995-04-07 1999-04-06 Schering Corporation Tricyclic compounds
US5712280A (en) * 1995-04-07 1998-01-27 Schering Corporation Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5703067A (en) * 1995-05-08 1997-12-30 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5710171A (en) * 1995-05-24 1998-01-20 Merck & Co., Inc. Bisphenyl inhibitors of farnesyl-protein transferase
US5972984A (en) * 1995-06-06 1999-10-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5756528A (en) * 1995-06-06 1998-05-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
NZ310778A (en) * 1995-06-07 1999-10-28 Glaxo Group Ltd Peptides and compounds that bind to a thrombopoietin receptor
US5663193A (en) * 1995-07-25 1997-09-02 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5703241A (en) * 1995-10-16 1997-12-30 Merck & Co., Inc. Inhibitor of farnesyl-protein transferase
GB2306646A (en) * 1995-10-30 1997-05-07 Merck & Co Inc Assay for compounds which inhibit ras oncogene activity involving farnesyl-protein transferase
US6221865B1 (en) 1995-11-06 2001-04-24 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
US6310095B1 (en) 1995-11-06 2001-10-30 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
US6204293B1 (en) 1995-11-06 2001-03-20 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
US6693123B2 (en) 1995-11-06 2004-02-17 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
GB9604311D0 (en) * 1996-02-29 1996-05-01 Merck & Co Inc Inhibitors of farnesyl-protein transferase
US6127366A (en) * 1995-11-22 2000-10-03 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5874442A (en) 1995-12-22 1999-02-23 Schering-Plough Corporation Tricyclic amides useful for inhibition of G-protein function and for treatment of proliferative disease
WO1997027852A1 (en) * 1996-01-30 1997-08-07 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US6028201A (en) * 1996-01-30 2000-02-22 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5968965A (en) * 1996-01-30 1999-10-19 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5981562A (en) * 1996-01-30 1999-11-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
WO1997027854A1 (en) * 1996-01-30 1997-08-07 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US7091311B2 (en) 1996-06-07 2006-08-15 Smithkline Beecham Corporation Peptides and compounds that bind to a receptor
US5767274A (en) * 1996-06-28 1998-06-16 Biomeasure, Incorporated Prenyl transferase inhibitors
US6238881B1 (en) * 1996-11-06 2001-05-29 Onyx Pharmaceuticals, Inc. Nucleic acids and polypeptides related to a guanine exchange factor of Rho GTPase
US6015817A (en) * 1996-12-05 2000-01-18 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5972966A (en) * 1996-12-05 1999-10-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5977134A (en) * 1996-12-05 1999-11-02 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5932590A (en) * 1996-12-05 1999-08-03 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US6060038A (en) * 1997-05-15 2000-05-09 Merck & Co., Inc. Radiolabeled farnesyl-protein transferase inhibitors
US5789438A (en) * 1997-09-05 1998-08-04 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
AU9005398A (en) * 1997-09-11 1999-03-29 Yuhan Corporation Thiourea derivatives or non-toxic salts thereof for inhibitng ras-transformed cell growth
SK284723B6 (en) * 1998-07-06 2005-10-06 Janssen Pharmaceutica N. V. Use of farnesyl protein transferase inhibitor for the preparation of pharmaceutical composition having radiosensitizing properties
US6423519B1 (en) * 1998-07-15 2002-07-23 Gpc Biotech Inc. Compositions and methods for inhibiting fungal growth
US5869275A (en) * 1998-07-20 1999-02-09 Huang; Eric Z. Affinity ultrafiltration assay for transferase activity
US8283315B2 (en) * 1998-08-28 2012-10-09 Lytix Biopharma As Inhibition of tumour growth
GB9818938D0 (en) 1998-08-28 1998-10-21 Alpharma As Bioactive peptides
WO2000075135A1 (en) * 1999-06-09 2000-12-14 Merck & Co., Inc. Biaryl inhibitors of prenyl-protein transferase
US6458935B1 (en) 1999-06-23 2002-10-01 Merck & Co., Inc. Radiolabeled farnesyl-protein transferase inhibitors
WO2001007437A1 (en) * 1999-07-21 2001-02-01 Merck & Co., Inc. Crystal forms of 1-(3-chlorophenyl)-4-[1-(4-cyanobenzyl)-5-imidazolylmethyl]-2-piperazinone
US6333335B1 (en) 1999-07-23 2001-12-25 Merck & Co., Inc. Phenyl-protein transferase inhibitors
US7074921B2 (en) * 2001-11-13 2006-07-11 Bristol Myers Squibb Company Process for the preparation of 3,7-disubstituted-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine compounds
ES2781475T3 (en) 2002-09-18 2020-09-02 Janssen Pharmaceuticals Inc Methods to increase the production of hematopoietic stem cells and platelets
DK1675606T3 (en) * 2003-08-28 2017-06-19 Janssen Pharmaceuticals Inc Peptides and compound that bind to thrombopoietin receptors
US7723295B2 (en) * 2003-08-28 2010-05-25 Ortho-Mcneil Pharmaceutical, Inc. Peptides and compounds that bind to a receptor
WO2005051392A1 (en) 2003-11-20 2005-06-09 Children's Hospital Medical Center Gtpase inhibitors and methods of use
US20060210542A1 (en) * 2004-08-16 2006-09-21 Yurkow Edward J Use of TPO mimetic compounds and pharmaceutical compositions in the treatment of anemia
WO2007016539A2 (en) 2005-07-29 2007-02-08 Children's Hospital Medical Center Gtpase inhibitors and methods of use and crystal structure of rac-1 gtpase
WO2009051772A1 (en) * 2007-10-17 2009-04-23 Duke University Geranylgeranyl transferase inhibitors and methods of making and using the same
US9980942B2 (en) 2012-05-02 2018-05-29 Children's Hospital Medical Center Rejuvenation of precursor cells
US10028503B2 (en) 2014-06-18 2018-07-24 Children's Hospital Medical Center Platelet storage methods and compositions for same
CN104744564B (en) * 2015-03-13 2017-07-28 天津托普泰克生物科技有限公司 Anti-hepatitis B virus X protein polypeptide drugs

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5055487A (en) * 1990-03-21 1991-10-08 Merck & Co., Inc. Novel anti-fungal compounds
US5043268A (en) * 1990-05-04 1991-08-27 The Trustees Of Princeton University Substrates and inhibitors for prenyl cysteine methyltransferase enzymes
US5026554A (en) * 1990-09-13 1991-06-25 Merck & Co., Inc. Method of inhibiting fungal growth using squalene synthetase inhibitors
US5283256A (en) † 1992-07-22 1994-02-01 Merck & Co., Inc. Cholesterol-lowering agents

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