Methods to mobilize progenitor/stem cells
First Claim
1. A method to obtain progenitor and/or stem cells from a subject which method comprises (a) administering to said subject a compound of the formula
Z-linker-Z′
-
(1) or pharmaceutically acceptable salt or prodrug form thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 2-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;
or Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′
is either embodied in a form as defined by Z above, or is of the formula
—
N(R)—
(CR2)n—
X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan;
“
linker”
represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, and/or oxygen atoms contained in an alkylene chain, and/or may contain keto groups and/or nitrogen or sulfur atoms;
in an amount effective to mobilize said progenitor and/or stem cells into the peripheral blood of said subject;
followed by (b) harvesting said progenitor and/or stem cells.
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Accused Products
Abstract
Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula
Z-linker-Z′ (1) or pharmaceutically acceptable salt thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;
or Z is of the formula
—N(R)—(CR2)n—X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan; “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.
25 Citations
28 Claims
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1. A method to obtain progenitor and/or stem cells from a subject which method comprises
(a) administering to said subject a compound of the formula
Z-linker-Z′-
(1)or pharmaceutically acceptable salt or prodrug form thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 2-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;
or Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′
is either embodied in a form as defined by Z above, or is of the formula
—
N(R)—
(CR2)n—
Xwherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan;
“
linker”
represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, and/or oxygen atoms contained in an alkylene chain, and/or may contain keto groups and/or nitrogen or sulfur atoms;
in an amount effective to mobilize said progenitor and/or stem cells into the peripheral blood of said subject;
followed by(b) harvesting said progenitor and/or stem cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
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28. A method to obtain progenitor and/or stem cells from a subject which method comprises
(a) administering to said subject an amount of a compound that binds to the chemokine receptor CXCR4 sufficient to mobilize said progenitor and/or stem cells into the peripheral blood of said subject; - followed by
(b) harvesting said progenitor and/or stem cells.
- followed by
Specification