Abstract: Disclosed herein is a compound of formula (I), which is ammonium salt of GW5074, wherein R1, R2, and R3 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl; or R1, R2, R3 and 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, —NH2, and —NRaRb, in which Ra and Rb are 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.

Abstract: Disclosed herein is a compound of formula (I), which is ammonium salt of GW5074, wherein R1, R2, and R3 are independently hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl; or R1, R2, R3 and 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, —NH2, and —NRaRb, in which Ra and Rb are 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.

Abstract: A pharmaceutical composition comprising sorafenib and GW5074. Said combination therapy inhibits cancer cell growth via c-Raf-PP2A-DAPK signaling transduction pathway in either in vitro or in preclinical animal model for orthotopic spontaneous kidney cancer which simulates clinical symptoms. Formation of the bond between c-Raf and GW5074 leads to conformational change which consequently increases the affinity between sorafenib and c-Raf. Binding with the specific drug target facilitates serine 308 dephosphorylation of DAPK by PP2A and induces necrosis in cancer cells. Serine 308 of DAPK protein may also be used as a biomarker for drug screening. This study provides a novel pharmaceutical composition comprising sorafenib and GW5074, a protein complex target consisting of c-Raf and DAPK for drug designing, as well as biomarkers including c-Raf protein, DAPK protein and phosphorylation status of DAPK for drug screening.

Abstract: A pharmaceutical composition comprising sorafenib and GW5074. Said combination therapy inhibits cancer cell growth via c-Raf-PP2A-DAPK signaling transduction pathway in either in vitro or in preclinical animal model for orthotopic spontaneous kidney cancer which simulates clinical symptoms. Formation of the bond between c-Raf and GW5074 leads to conformational change which consequently increases the affinity between sorafenib and c-Raf. Binding with the specific drug target facilitates serine 308 dephosphorylation of DAPK by PP2A and induces necrosis in cancer cells. Serine 308 of DAPK protein may also be used as a biomarker for drug screening. This study provides a novel pharmaceutical composition comprising sorafenib and GW5074, a protein complex target consisting of c-Raf and DAPK for drug designing, as well as biomarkers including c-Raf protein, DAPK protein and phosphorylation status of DAPK for drug screening.

Abstract: A pharmaceutical composition comprising sorafenib and GW5074. Said combination therapy inhibits cancer cell growth via c-Raf-PP2A-DAPK signaling transduction pathway in either in vitro or in preclinical animal model for orthotopic spontaneous kidney cancer which simulates clinical symptoms. Formation of the bond between c-Raf and GW5074 leads to conformational change which consequently increases the affinity between sorafenib and c-Raf. Binding with the specific drug target facilitates serine 308 dephosphorylation of DAPK by PP2A and induces necrosis in cancer cells. Serine 308 of DAPK protein may also be used as a biomarker for drug screening. This study provides a novel pharmaceutical composition comprising sorafenib and GW5074, a protein complex target consisting of c-Raf and DAPK for drug designing, as well as biomarkers including c-Raf protein, DAPK protein and phosphorylation status of DAPK for drug screening.

Abstract: A pharmaceutical composition comprising sorafenib and GW5074. Said combination therapy inhibits cancer cell growth via c-Raf-PP2A-DAPK signaling transduction pathway in either in vitro or in preclinical animal model for orthotopic spontaneous kidney cancer which simulates clinical symptoms. Formation of the bond between c-Raf and GW5074 leads to conformational change which consequently increases the affinity between sorafenib and c-Raf. Binding with the specific drug target facilitates serine 308 dephosphorylation of DAPK by PP2A and induces necrosis in cancer cells. Serine 308 of DAPK protein may also be used as a biomarker for drug screening. This study provides a novel pharmaceutical composition comprising sorafenib and GW5074, a protein complex target consisting of c-Raf and DAPK for drug designing, as well as biomarkers including c-Raf protein, DAPK protein and phosphorylation status of DAPK for drug screening.

Abstract: A pharmaceutical composition is provided which includes sorafenib and GW5074. This combination therapy inhibits cancer cell growth via c-Raf-PP2A-DAPK signaling transduction pathway in either an in vitro or pre-clinical animal model for orthotopic spontaneous kidney cancer which simulates clinical symptoms. Formation of the bond between c-Raf and GW5074 leads to conformational change which consequently increases the affinity between sorafenib and c-Raf. Binding with the specific drug target facilitates serine 308 dephosphorylation of DAPK by PP2A and induces necrosis in cancer cells. Serine 308 of DAPK protein may also be used as a biomarker for drug screening. A novel pharmaceutical composition is provided which includes sorafenib and GW5074, a protein complex target consisting of c-Raf and DAPK for drug designing, as well as biomarkers including c-Raf protein, DAPK protein and phosphorylation status of DAPK for drug screening.

Abstract: Methods and pharmaceutical compositions for treating cancer utilizing compounds characterized by the following structure: and their pharmaceutically acceptable salts.

Abstract: Methods and pharmaceutical compositions for treating cancer utilizing compounds characterized by the following structure: and their pharmaceutically acceptable salts.