National Defense Medical Center

Metagone Biotech Inc.

Tai-Lung Cha

Yi-Ta Tsai

Chung-Chih Lin

Sun-Yran Chang

Guang-Huan Sun

Hsu-Shan Huang

Tsung-Chih Chen

Sheng-Chieh Lin

Tai-Wei Ly

Yun Yu

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, &#x2014;OH, &#x2014;NH, and &#x2014;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.

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

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.

Pharmaceutical compositions and methods for treating cancer and biomarkers for drug screening

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

Heteroannelated anthraquinone derivatives for inhibiting cancers

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Taipei, Taiwan

Tai-Lung Cha