Methods and compositions for stimulating the proliferation or differentiation of stem cells with substance P or an analog thereof
OwnerHal Siegel, Kasey L. Bensoninventors
Life of this patent
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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.