Methods and Compositions for Stimulating the Proliferation or Differentiation of Stem Cells with Substance Por an Analog Thereof
AssigneeImmuneRegen Biosciences, Inc.
InventorsHal N. Siegel, Kasey L. Benson
Life of this patent
Estimating the term…
Abstract
Compositions and methods are provided for stimulating cell proliferation and differentiation with substance P or a substance P analog. In one embodiment, the methods provide for stimulating or promoting stem cell differentiation by contacting a stem cell with substance P or a substance P analog. In another embodiment, the methods provide for administering to subject an effective amount of substance P or a substance P analog to treat an illness, disease or disorder.
Claims31
A method of treating or ameliorating a stem cell disorder comprising administering to a subject an effective amount of a substance P analog;
- wherein the substance P analog is of Formula (I):
- (SEQ ID NO:
- 11)
- Z1-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-
- Xaa10-Xaa11-Z2 (I)
- or a pharmaceutically acceptable salt thereof, wherein:
- Xaa1 is Arg, Lys, 6-N methyllysine or (6-N,6-N)dimethyllysine;
- Xaa2 is Pro or Ala;
- Xaa3 is Lys, Arg, 6-N-methyllysine or (6-N,6-N)dimethyllysine;
- Xaa4 is Pro or Ala;
- Xaa5 is Gln or Asn;
- Xaa6 is Gln or Asn;
- Xaa7 is Tyr, Phe or Phe substituted with chlorine at position 2, 3 or 4;
- Xaa8 is Tyr, Phe, or Phe substituted with chlorine at position 2, 3 or 4;
- Xaa9 is Gly, Pro, Ala or N-methylglycine;
- Xaa10 is Leu, Val, Ile, Norleucine, Met, Met sulfoxide, Met sulfone, N-methylleucine, or N-methylvaline;
- Xaa11 is Met, Met sulfoxide, Met sulfone, or Norleucine;
- Z1 is R2N— or RC(O)NR—;
- Z2 is —C(O)NR2 or —C(O)OR or a salt thereof;
- each R is independently —H, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, (C5-C20) aryl, (C6-C26) alkaryl, 5-20 membered heteroaryl or 6-26 membered alkheteroaryl;
- and
- each “-” between residues Xaa1 through Xaa11 independently designates an amide linkage, a substitute amide linkage or an isostere of an amide.
A composition comprising a cell and a substance P analog in an amount effective to stimulate differentiation of the cell wherein the substance P analog is of Formula (I):
- (SEQ ID NO:
- 11)
- Z1-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-
- Xaa10-Xaa11-Z2 (I)
- or a pharmaceutically acceptable salt thereof, wherein:
- Xaa1 is Arg, Lys, 6-N methyllysine or (6-N,6-N)dimethyllysine;
- Xaa2 is Pro or Ala;
- Xaa3 is Lys, Arg, 6-N-methyllysine or (6-N,6-N)dimethyllysine;
- Xaa4 is Pro or Ala;
- Xaa5 is Gln or Asn;
- Xaa6 is Gln or Asn;
- Xaa7 is Tyr, Phe or Phe substituted with chlorine at position 2, 3 or 4;
- Xaa8 is Tyr, Phe, or Phe substituted with chlorine at position 2, 3 or 4;
- Xaa9 is Gly, Pro, Ala or N-methylglycine;
- Xaa10 is Leu, Val, Ile, Norleucine, Met, Met sulfoxide, Met sulfone, N-methylleucine, or N-methylvaline;
- Xaa11 is Met, Met sulfoxide, Met sulfone, or Norleucine;
- Z1 is R2N— or RC(O)NR—;
- Z2 is —C(O)NR2 or —C(O)OR or a salt thereof;
- each R is independently —H, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, (C5-C20) aryl, (C6-C26) alkaryl, 5-20 membered heteroaryl or 6-26 membered alkheteroaryl;
- and
- each “-” between residues Xaa1 through Xaa11 independently designates an amide linkage, a substitute amide linkage or an isostere of an amide.
A composition for promoting wound healing comprising cells, a matrix, and a substance P analog wherein the substance P analog is of Formula (I):
- (SEQ ID NO:
- 11)
- Z1-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-
- Xaa10-Xaa11-Z2 (I)
- or a pharmaceutically acceptable salt thereof, wherein:
- Xaa1 is Arg, Lys, 6-N methyllysine or (6-N,6-N)dimethyllysine;
- Xaa2 is Pro or Ala;
- Xaa3 is Lys, Arg, 6-N-methyllysine or (6-N,6-N)dimethyllysine;
- Xaa4 is Pro or Ala;
- Xaa5 is Gln or Asn;
- Xaa6 is Gln or Asn;
- Xaa7 is Tyr, Phe or Phe substituted with chlorine at position 2, 3 or 4;
- Xaa8 is Tyr, Phe, or Phe substituted with chlorine at position 2, 3 or 4;
- Xaa9 is Gly, Pro, Ala or N-methylglycine;
- Xaa10 is Leu, Val, Ile, Norleucine, Met, Met sulfoxide, Met sulfone, N-methylleucine, or N-methylvaline;
- Xaa11 is Met, Met sulfoxide, Met sulfone, or Norleucine;
- Z1 is R2N— or RC(O)NR—;
- Z2 is —C(O)NR2 or —C(O)OR or a salt thereof;
- each R is independently —H, (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, (C5-C20) aryl, (C6-C26) alkaryl, 5-20 membered heteroaryl or 6-26 membered alkheteroaryl;
- and
- each “-” between residues Xaa1 through Xaa11 independently designates an amide linkage, a substitute amide linkage or an isostere of an amide.
Dependencies are inferred from the claim text.