Ammonium salts of 3-(3,5-dibromo-4-hydroxybenzyliden)-5-indo-1,3-dihydroindol-2-one and uses thereof

Abstract

Disclosed herein is a compound of formula (I), which is ammonium salt of GW5074, wherein R, R, and Rare independently hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl; or R, R, Rand the nitrogen are taken together to form a 6-membered heterocyclyl; and the alkyl, the alkenyl, the alkynyl, the aryl, the heteroaryl, or the 6-membered heterocyclyl is optionally substituted with at least one substituent selected from the group consisting of, —OH, —NH, and —NRR, in which Rand Rare independently alkyl, aryl, or heteroaryl. Also disclosed herein is a pharmaceutical kit for the treatment of cancers. The pharmaceutical kit includes, a first formulation comprising a c-Raf inhibitor and a pharmaceutically acceptable carrier; and a second formulation comprising the compound of formula (I) and a pharmaceutically acceptable carrier. Also encompasses herein is a method of treating a subject having a cancer. The method comprises: (a) detecting whether the cancer cells of the subject has phosphorylation on serine 308 of death-associated protein kinase (DAPK); and (b) treating the subject based on the detection of the step (a) by, administering to the subject (i) an effective amount of a c-Raf inhibitor, and (ii) an effective amount of the compound of formula (I), when the phosphorylation on serine 308 of DAPK in the cancer cells is detected.