Compounds that inhibit the binding of RAF-1 or 14-3-3 proteins to the beta chain of IL-2 receptor, and pharmaceutical compositions containing same

• US 6,281,193 B1
• Filed: 03/08/1999
• Issued: 08/28/2001
• Est. Priority Date: 05/23/1996
• Status: Expired due to Fees

• Current Assignee: Applied Research Systems ARS Holding NV (Merck & Co., Inc.)
• Original Assignee: Applied Research Systems ARS Holding NV (Merck & Co., Inc.)
• Inventors: Strom, Terry, Maslinski, Wlodzimierz
• Primary Examiner(s): Saunders, David
• Assistant Examiner(s): DECLOUX, AMY M
• Application Number:
  US09/194,145
• Publication Number:
  US 20010016194A1
• Time in Patent Office: 904 Days
• Field of Search: 530/300, 530/350, 530/387.9, 530/388.1, 530/388.22, 530/389.1, 530/324, 530/402, 424/139.1, 424/143.1, 424/185.1, 424/278.1, 424/810, 514/1, 514/2, 514/8, 514/12
• US Class Current: 514/21.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 14/4705 stimulating, promoting or activating activity
• CPC Class Codes: C07K 14/7155 for interleukins [IL]
• CPC Class Codes: C12N 9/1205 Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
• CPC Class Codes: C12Q 1/485 involving kinase
• CPC Class Codes: G01N 2500/04 Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: Y10S 424/81 involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, immunotolerance, or anergy

Abstract

The invention relates to compounds, such as proteins, peptides and organic compounds, capable of blocking or inhibiting the binding interaction of Raf-1 or 14-3-3 proteins to the β chain of IL-2, and pharmaceutical compositions containing such compounds. In vitro assays for isolating, identifying and characterizing such compound capable of inhibiting interaction of Raf-1 or 14-3-3 proteins to IL-2β are also provided.

Claims

1. A compound capable of disrupting the binding of Raf-1 protein and 14-3-3 to IL-2Rβ

and selected from the group consisting of a peptide having the amino acid sequence corresponding to residues 370 to 396 of SEQ ID NO;

2, an analog of said peptide where one amino acid residue of residues 370 to 396 of SEQ ID NO;

2 is replaced with a different amino acid residue or deleted, and a chemical derivative of said peptide which enhances the peptide'"'"'s permeability across the cell membrane or facilitates the transport of the Peptide through the membrane into the cytoplasm, wherein said compound is not a full length human IL-2Rβ

chain.

2. A composition comprising:

a compound according to claim 1 or a mixture of two or more different compounds according to claim 1; and

a pharmaceutically acceptable carrier, excipient or diluent.