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Yanggu, South Korea

Hwang J.J.,University of Ulsan | Kim Y.S.,University of Ulsan | Kim T.,University of Ulsan | Kim M.J.,University of Ulsan | And 7 more authors.
Investigational New Drugs | Year: 2012

We synthesized a novel hydroxamate-based pan-histone deacetylase inhibitor (HDACI), CG200745 {(E)-2-(Naphthalen-1-yloxymethyl)-oct-2-enedioic acid 1- [(3-dimethylamino-propyl)-amide] 8-hydroxyamide]}. Like other inhibitors, for example vorinostat and belinostat, CG200745 has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Firstly, we analyzed its inhibitory activity against histone deacetylase (HDAC) in hormone-dependent LNCaP cells and hormone-independent DU145 and PC3 cells. CG200745 inhibited deacetylation of histone H3 and tubulin as much as vorinostat and belinostat did. CG200745 also inhibited growth of prostate cancer cells, increased sub-G1 population, and activated caspase-9, - 3 and -8 in LNCaP, DU145 and PC3 cells. These results indicate that CG200745 induces apoptosis. Next, we examined the effect of CG200745 on cell death induced by docetaxel in DU145 cells in vitro and in vivo. Compared to mono-treatment with each drug, pre-treatment of DU145 cells with docetaxel followed by CG200745 showed synergistic cytotoxicity, and increased the apoptotic sub-G1 population, caspase activation, and tubulin acetylation. Moreover, the combination treatment decreased Mcl-1 and Bcl- XL. Docetaxel and CG200745 combination reduced tumor size in the DU145 xenograft model. These preclinical results show that combination treatment with docetaxel and new HDACI, CG200745, potentiated anti-tumor effect in hormone-refractory prostate cancer (HRPC) cells via activation of apoptosis. © Springer Science+Business Media, LLC 2011. Source

Kim M.J.,University of Ulsan | Kim D.E.,University of Ulsan | Jeong I.G.,University of Ulsan | Choi J.,University of Ulsan | And 6 more authors.
Anticancer Research | Year: 2012

Aim: To investigate the anticancer effect of histone deacetylase inhibitors (HDACIs) in combination with sorafenib in wild-type and mutant von Hippel-Lindau (VHL)-expressing renal cell carcinomas (RCCs). Materials and Methods: We exposed clear cell RCC cells to HDACIs (vorinostat or belinostat) or sorafenib. We performed 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assays, western blotting, flow cytometry and enzyme-linked immunosorbent assays (ELISA) to evaluate mechanisms of cell death, and used CalcuSyn to analyze the potential synergism. Results: HDACIs alone inhibited the growth of clear cell RCC cell lines, increased acetylation of histone 3 and of tubulin, activated caspases-8, -9, and -3, and augmented the sub-G1 population, independently of VHL and permeability glycoprotein (P-gp). Moreover, pre-treatment of Caki-1 (wild-type VHL) and 786-O (mutant VHL) with HDACIs followed by sorafenib reduced cell viability synergistically via activation of caspases and downregulation of the levels of myeloid leukemia cell differentiation protein (MCL1), phospho-extracellular signal-regulated kinase (ERK), and secreted vascular endothelial growth factor (VEGF). Conclusion: Sorafenib is more effective in combination with HDACIs even for clear cell RCCs harboring mutant VHL. Source

The present invention provides a compound selected from the group consisting of a compound of formula (I), pharmaceutically acceptable salts, esters, prodrugs, hydrates, solvates and isomers thereof; a use of the compound for the treatment, relief or prevention of diseases caused by abnormal or uncontrolled activation of protein kinase, and a use of the compound for the manufacture of a medicament for the treatment, relief or prevention of the diseases; a pharmaceutical composition comprising the compound as an active ingredient; and a method for the treatment, relief or prevention of the diseases using the compound. The inventive compound is useful for the treatment, relief or prevention of diseases caused by abnormal or uncontrolled activation of protein kinase.

News Article | February 9, 2015
Site: www.fiercebiotech.com

SINGAPORE--CrystalGenomics signed a sales and marketing deal with South Korea's Daewoong Pharmaceutical for the commercialization of Acelex (polmacoxib), granting the South Korean firm exclusive rights in country for the osteoarthritis treatment. CrystalGenomics will receive an upfront payment and milestone payments from Daewoong and also share profits for a therapy initially aimed to capture at least 10% of the arthritis market in South Korea. Daewoong Pharmaceutical, one of the largest South Korean pharmaceutical companies, develops, manufactures, and commercializes pharmaceuticals and has the largest prescription drug sales in the Korean market. Currently, Daewoong commercializes 10 blockbuster products in various therapeutic areas including orthopedics and analgesics. Related Articles: S. Korean biotech snags financing with help from U.S. venture group Back end deal for CrystalGenomics

CrystalGenomics Inc. and Sbi Biotech Co. | Date: 2011-06-29

The present invention provides a (di)azaindole derivative represented by the formula (I). A compound of the present invention inhibits a Cdc7 protein kinase activity and suppresses cell proliferation.

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