Abcb5 ligands and substrates
AssigneeChildren's Medical Center Corporation
InventorMarkus H. Frank
Life of this patent
Estimating the term…
Abstract
The present invention is directed to methods and compositions for modulating ABCB5+ stem cell activity. The invention also relates to assays and reagents for manipulating and characterizing compounds that modulate ABCB5+ cell signaling.
Claims27
A method of enhancing ABCB5-positive cell function,
- comprising administering to a subject in need thereof an effective amount of a composition that enhances ABCB5-PIP2 pathway and thus promotes wound healing, tissue regeneration, angiogenesis, or cell survival, and wherein the composition comprises a synthetic phospholipid, comprising a compound having the structure:
- wherein the phospholipid comprises two fatty acids, wherein each of the fatty acids comprises a carboxyl linked to a carbon atom chain identified by R1 and R2 and wherein R1 and R2 independent of one another have a length defined by a number of carbon atoms acid chains;
- wherein one of R1 and R2 has a length that is at least twice as long as the other of R1 and R2.
2-7. (canceled)
(canceled)
15-17. (canceled)
A method of inhibiting ABCB5-positive cancer cell function, comprising administering to a subject in need thereof an effective amount of a composition that inhibits ABCB5-PIP2 binding wherein the composition is selected from a group comprising a small molecule, a lipid analog, an anti-ABCB5 antibody or fragment having specificity for the cyclical form or the linear form of an extracellular polypeptide of the protein, an enzyme, and an anti-ABCB5 antibody or fragment thereof that alters the conformation of ABCB5 PIP2 binding site.
19-30. (canceled)
A method for identifying an enhancer or inhibitor of ABCB5-PIP2 pathway, comprising,
- contacting an ABCB5+ cell with a putative composition that modulates ABCB5-PIP2 binding;
- determining a level of a PIP2 pathway product compound and comparing the level with a baseline level of the PIP2 pathway product compound, wherein if the level is greater than the baseline level, the putative composition is an ABCB5-PIP2 pathway enhancer and if the level of PIP2 pathway product compound is lower than the baseline level, the putative composition is an ABCB5-PIP2 inhibitor.
(canceled)
34-38. (canceled)
A composition comprising a synthetic phospholipid, comprising a compound having the structure:
- wherein R1 and R2 are independent fatty acid chains;
- and
- wherein R1 and R2 have a length that is at least twice as long as the other of R1 and R2.
47-71. (canceled)
A method for treating a cancer in a subject, comprising:
- administering to the subject an ABCB1 inhibitor in an effective amount to inhibit ABCB5-PIP2 pathway function to treat the cancer in the subject, wherein:
- i) the cancer is comprised of cancer cells and the cancer cells express negligible or no ABCB1;
- or
- ii) the method further comprises detecting the presence of an ABCB5+ stem cell prior to the administration step;
- or
- iii) wherein the ABCB1 inhibitor is a pump inhibitor and the cancer is not concurrently treated with a chemotherapeutic agent;
- or
- iv) the method further comprises assessing ABCB5-PIP2 binding following administration of the composition.
73-75. (canceled)
Dependencies are inferred from the claim text.