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US 10,864,248 B2Granted
Dab2 inhibitors for the prevention and treatment of cystic fibrosis
AssigneeTrustees of Dartmouth College
InventorDean R. Madden
Life of this patent
Estimating the term…
Abstract
Compositions and kits including an agent that inhibits the interaction between Disabled-2 and mutant CFTR proteins, optionally in combination with a CFTR corrector, CFTR potentiator, CAL inhibitor, mucolytic, anti-inflammatory agent or a combination thereof are provided as are methods for preventing or treating cystic fibrosis.
Claims14
A peptide for inhibiting the interaction between a degradation-prone Cystic Fibrosis Transmembrane Conductance Regulator and Disabled-2 comprising the amino acid sequence of SEQ ID NO:2.
A pharmaceutical composition comprising
- (i) a pharmaceutically acceptable carrier in admixture with a compound of Formula II, or hydrate, prodrug or pharmaceutically acceptable salt thereof:
- wherein
- R1 is present or absent, and when present is a substituent on one or more ring atoms and is for each ring atom independently a hydroxyl group, a halo group, or a substituted or unsubstituted lower alkyl or alkoxy group;
- R2, R3 and R6 are independently present or absent and when present independently represent hydrogen or a substituted or unsubstituted lower alkyl;
- and
- R4 is ═O or ═S;
- and
- (ii) a CFTR corrector, CFTR potentiator, CAL inhibitor, mucolytic, anti-inflammatory agent or a combination thereof.
5 more elements
A pharmaceutical composition comprising
- (i) a pharmaceutically acceptable carrier in admixture with a compound of Formula III, or hydrate, prodrug or pharmaceutically acceptable salt thereof:
- wherein
- R1 is present or absent, and when present is a substituent on one or more ring atoms and is for each ring atom independently a hydroxyl group, a halo group, or a substituted or unsubstituted lower alkyl or alkoxy group;
- R2, R3, R4, R5 and R6 are independently present or absent and when present independently represent hydrogen or a substituted or unsubstituted lower alkyl;
- or
- R4 together with R3 or R5 form a substituted or unsubstituted cycloalkyl or heterocycloalkyl group;
- R7 is a substituted or unsubstituted lower alkyl;
- and
- dashed bonds are independently present or absent;
- and
- (ii) a CFTR corrector, CFTR potentiator, CAL inhibitor, mucolytic, anti-inflammatory agent or a combination thereof.
8 more elements
A kit comprising
- (a) an agent that inhibits the interaction between a degradation-prone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Disabled-2, wherein said agent comprises:
- (i) a peptide having the amino acid sequence of SEQ ID NO:2,
- (ii) a compound has the structure of Formula II:
- wherein
- R1 is present or absent, and when present is a substituent on one or more ring atoms and is for each ring atom independently a hydroxyl group, a halo group, or a substituted or unsubstituted lower alkyl or alkoxy group;
- R2, R3 and R6 are independently present or absent and when present independently represent hydrogen or a substituted or unsubstituted lower alkyl;
- and
- R4 is ═O or ═S, or
- (iii) a compound has the structure of Formula III:
- wherein
- R1 is present or absent, and when present is a substituent on one or more ring atoms and is for each ring atom independently a hydroxyl group, a halo group, or a substituted or unsubstituted lower alkyl or alkoxy group;
- R2, R3, R4, R5 and R6 are independently present or absent and when present independently represent hydrogen or a substituted or unsubstituted lower alkyl;
- or
- R4 together with R3 or R5 form a substituted or unsubstituted cycloalkyl or heterocycloalkyl group;
- R7 is a substituted or unsubstituted lower alkyl;
- and
- dashed bonds are independently present or absent;
- and
- (b) a CFTR corrector, CFTR potentiator, CAL inhibitor, mucolytic, anti-inflammatory agent or a combination thereof.
16 more elements
A method for treating cystic fibrosis comprising administering to a subject in need thereof a pharmaceutical composition comprising:
- (i) a peptide having the amino acid sequence of SEQ ID NO:2,
- (ii) a compound has the structure of Formula II:
- wherein
- R1 is present or absent, and when present is a substituent on one or more ring atoms and is for each ring atom independently a hydroxyl group, a halo group, or a substituted or unsubstituted lower alkyl or alkoxy group;
- R2, R3 and R6 are independently present or absent and when present independently represent hydrogen or a substituted or unsubstituted lower alkyl;
- and
- R4 is ═O or ═S, or
- (iii) a compound has the structure of Formula III:
- wherein
- R1 is present or absent, and when present is a substituent on one or more ring atoms and is for each ring atom independently a hydroxyl group, a halo group, or a substituted or unsubstituted lower alkyl or alkoxy group;
- R2, R3, R4, R5 and R6 are independently present or absent and when present independently represent hydrogen or a substituted or unsubstituted lower alkyl;
- or
- R4 together with R3 or R5 form a substituted or unsubstituted cycloalkyl or heterocycloalkyl group;
- R7 is a substituted or unsubstituted lower alkyl;
- and
- dashed bonds are independently present or absent, thereby treating the subject's cystic fibrosis.
13 more elements
Dependencies are inferred from the claim text.