Dab2 inhibitors for the prevention and treatment of cystic fibrosis
AssigneeTrustees of Dartmouth College
InventorDean R. MADDEN
Life of this patent
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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.
Claims20
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, or a derivative or peptidomimetic thereof.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier in admixture with a compound of Formula I, 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, R5 and R6 are independently present or absent and when present independently represent hydrogen or a substituted or unsubstituted lower alkyl;
- R4 is hydrogen, ═O or ═S;
- or
- R4 together with R3 or R5 form a substituted or unsubstituted cycloalkyl or heterocycloalkyl group;
- X1 is N or C;
- X2 is N, C or C—C or C═C;
- X3 is N, C or C—R7, wherein R7 is a substituted or unsubstituted lower alkyl;
- and
- dashed bonds are independently present or absent.
A kit comprising
- (a) an agent that inhibits the interaction between a degradation-prone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Disabled-2;
- and
- (b) a CFTR corrector, CFTR potentiator, CAL inhibitor, mucolytic, anti-inflammatory agent or a combination thereof.
The kit of claim 14, wherein the peptide is listed in Table 1.
Dependencies are inferred from the claim text.