Wan Chai, Hong Kong
Wan Chai, Hong Kong

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Wu M.-S.,Sun Yat Sen University | Wang G.-F.,Ascentage Pharma | Zhao Z.-Q.,Sun Yat Sen University | Liang Y.,Sun Yat Sen University | And 9 more authors.
Molecular Cancer Therapeutics | Year: 2013

Nasopharyngeal carcinoma is a common malignancy in Southern China. After radiotherapy and chemotherapy, a considerable proportion of patients with nasopharyngeal carcinoma suffered tumor relapse and metastasis. Cancer stemcells (CSC) have been shown with resistance against therapies and thus considered as the initiator of recurrence andmetastasis in tumors,where the antiapoptotic property ofCSCsplay an important role. Smac/DIABLO is an inverse regulator for the inhibitors of apoptosis protein family (IAP), which have been involved in apoptosis.Here, the effects ofSmac mimetics on the CSCs of nasopharyngeal carcinomawere studied both in vitro and in vivo, using two clones of nasopharyngeal carcinoma cell line CNE2 as models. We found that one of the clones, S18, had CSC-like properties and IAPs were overexpressed. The combination ofSmac mimetics and TNF-related apoptosis-inducing ligand (TRAIL) can reduce the percentage of SP cells and inhibit the colonyand sphere-forming abilities of S18 cells, indicating their ability to attenuate the CSCs. Moreover, in a nasopharyngeal carcinoma xenograft model, the administration of Smac mimetics in combination with TRAIL also led to the elimination of nasopharyngeal carcinoma stem cells. Furthermore, the Smac mimetics in combination with TRAIL induced the degradation of cIAP1 and XIAP and thus induced apoptosis in vitro and in vivo. Taken together, our data show that Smac mimetics exerted an antitumor effect on nasopharyngeal carcinomacancer stemcells, and this combination treatment should be considered as a promising strategy for the treatment of nasopharyngeal carcinoma. © 2013 American Association for Cancer Research.

News Article | April 27, 2016
Site: www.rdmag.com

Google’s Calico, an institution with a mysterious mission to “cure death” could have competition from a new collaboration struck between Ascentage Pharma and Unity Biotechnology.Read more about New R&D Pact Seeks Cure for Aging-Related DiseasesComments

Sheng R.,University of Michigan | Sheng R.,Zhejiang University | Sun H.,University of Michigan | Liu L.,University of Michigan | And 19 more authors.
Journal of Medicinal Chemistry | Year: 2013

We have designed, synthesized, and evaluated a series of new compounds based upon our previously reported bivalent Smac mimetics. This led to the identification of compound 12 (SM-1200), which binds to XIAP, cIAP1, and cIAP2 with Ki values of 0.5, 3.7, and 5.4 nM, respectively, inhibits cell growth in the MDA-MB-231 breast cancer and SK-OV-3 ovarian cancer cell lines with IC50 values of 11.0 and 28.2 nM, respectively. Compound 12 has a much improved pharmacokinetic profile over our previously reported bivalent Smac mimetics and is highly effective in induction of rapid and durable tumor regression in the MDA-MB-231 xenograft model. These data indicate that compound 12 is a promising Smac mimetic and warrants extensive evaluation as a potential candidate for clinical development. © 2013 American Chemical Society.

Ascentage Pharma is dedicated to the R&D of novel drugs with focus on targeted anti-cancer small molecule drugs. Innovation in China, Benefit to the world

HongKongOffice Address:11/F,AXACentre,151GloucesterRoad,Wanchai,Hongkong Phone(852)28368170 Fax(852)30202124 TaizhouOffice Address:QB3Building,MedicalCityAvenue,Taizhou,Jiangsu Zipcode:225300 Phone:(86)-523-6201369 Fax:(86)-523-6201369 ShanghaiOffice Address:Room205,No.1118,HaleiRoad,ZhangjiangHi-TechPark,Pudong,Shanghai Zipcode:201203 Phone:(86)-21-51320528 Fax(86)-21-51320512

Ascentage Pharma, a clinical-stage biopharmaceutical company focused on apoptosis-targeted oncology drug discovery and development, and UNITY Biotechnology, aSan Francisco-based biopharmaceutical company focused on the development of medicines to improve healthspan, announced a worldwide collaboration to develop senolytic treatments for age-related disease. The Ascentage team has been working for over a decade to create small-molecule drugs targeting programmed cell death and has established a best-in-class compound library and clinical-stage lead compounds for oncology therapeutics ...

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Ascentage Pharma is dedicated to the R&D of novel drugs with focus on targeted anti-cancer small molecule drugs. Innovation in China, Benefit to the world

Ascentage Pharma is a leading company in innovative drugs research and development in China. Its experienced and energetic team is talented and self-motivated about the R&D of first-in-class and best-in-class drugs ...

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