Cancer treatment with gamma-secretase inhibitors
AssigneeThe Johns Hopkins University
InventorsCharles Eberhart, Xing Fan, Anirban Maitra
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Abstract
Provided are methods for treating cancer in a patient, comprising administering to a patient in need thereof a therapeutically effective regimen, the regimen comprising administering a gamma-secretase inhibitor, wherein the regimen results in a reduction in the cancer cell population in the patient. In some embodiments of the methods, the therapeutically effective regimen stabilizes, reduces or eliminates the cancer stem cell population. Also provided are compounds of the formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, and X are as herein described.
Claims67
A method of treating cancer in a human patient, comprising administering to a human patient in need thereof a therapeutically effective amount of a compound of the formula:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- X is halo;
- R1 is hydrogen, halogen, hydroxy, C1-6alkyl, or C1-4alkoxy;
- R2 is a radical of the following structure:
- wherein:
- E is CH2 or NH;
- D is (CH2)m, O(CH2)m, HN(CH2)n, or CH═CH;
- wherein m is 0, 1 or 2;
- A and Q are independently N, NCH3 or C;
- M is C or C═O;
- n is 1 or 2;
- Z1 and Z2 are independently H, halo, halo(C1-4)alkyl, phenyl, or
- Z1 and Z2, when attached to carbon atoms, form a 6-membered aryl ring with the carbon atoms to which they are attached;
- and
- Z3 is H, halo, halo(C1-4)alkyl, or phenyl.
A method of treating cancer in a human patient, comprising administering to a human patient in need thereof a therapeutically effective regimen, the regimen comprising administering a gamma-secretase inhibitor, wherein the regimen results in a reduction in the cancer cell population in the patient.
Dependencies are inferred from the claim text.