Methods for SHP1 mediated neuroprotection

• US 7,129,267 B2
• Filed: 03/11/2003
• Issued: 10/31/2006
• Est. Priority Date: 03/11/2002
• Status: Expired due to Fees

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Renzi, Michael, Farrell, Francis X., Thirumalai, Navneeth, Jolliffe, Linda
• Primary Examiner(s): Andres, Janet L.
• Assistant Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US10/386,243
• Publication Number:
  US 20030232749A1
• Time in Patent Office: 1,330 Days
• Field of Search: 514/438, 514/369
• US Class Current: 514/438
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: C12Q 1/44 involving esterase
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• 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 2500/10 involving cells
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes

Abstract

The effect of EPO on the phosphorylation of the EPO receptor, the activation of the MAP Kinase pathway, and the expression of SHP-1 were analyzed. EPO was observed to cause a decrease in the expression of its negative regulator SHP-1. The decrease observed at both the mRNA and protein level was dose dependent and persisted as long as 24 hr following EPO treatment. EPO can down regulate the expression of its own negative regulator as a means for increased potency in neurons. Assays were generated to identify compounds that are useful in regulating SHP1 activity in neural cells.

Claims

1. A method for increasing the potency of erythropoietin (EPO) in a subject in need thereof, comprising the step of administering to the subject an effective dose of a composition that decreases the tyrosine phosphatase activity of SHP1 in a cell of the nervous system of the subject, wherein said composition is selected from the group consisting of a compound of Formula (I);