38 results about "CXCR4 antagonist" patented technology

A composition including a CXCR4 antagonist and a CCR5 antagonist represented by formula I or II: or an acceptable salt, solvate or ester thereof. The CXCR4 antagonist includes at least one of AMD-070, CS-3955, KRH-1120, KRH-2731, and KRH-1636.

The chemokine receptor CXCR4 is a co-receptor for T-tropic strains of HIV-1. A number of small molecule antagonists of CXCR4 are in development, but all are likely to lead to adverse effects due to the physiological function of CXCR4. To prevent these complications, allosteric agonists may be therapeutically useful as adjuvant therapy in combination with small molecule antagonists. A synthetic cDNA library coding for 160,000 different SDF-based peptides was screened for CXCR4 agonist activity in a yeast strain expressing functional receptor. Peptides that activated CXCR4 in an autocrine manner induced colony formation. Two peptides, designated RSVM and ASLW, were identified as novel agonists that are insensitive to the CXCR4 antagonist AMD3100. In chemotaxis assays using the acute lymphoblastic leukemia cell line CCRF-CEM, RSVM behaves as a partial agonist and ASLW as a superagonist. The superagonist activity of ASLW may be related to its inability to induce receptor internalization. In CCRF-CEM cells, the two peptides are also not inhibited by another CXCR4 antagonist, T140, or the neutralizing monoclonal antibodies 12G5 and 44717.111. These results suggest that alternative agonist binding sites are present on CXCR4 that could be screened to develop molecules for therapeutic use.

In accordance with various aspects of the invention, CXCR4 antagonists may be used to treat hematopoietic cells, such as progenitor or stem cells, to promote the rate of cellular multiplication, self-renewal, proliferation or expansion. CXCR4 antagonists may be used therapeutically to stimulate hematopoietic stem / progenitor cell multiplication / self-renewal.

Presently disclosed are methods and compositions for treating or preventing WHIM syndrome and certain other disorders or conditions with a certain CXCR4 antagonist.