News Article | September 25, 2017
Dr. Huang has over twenty years of clinical cancer research and drug development experience in the biopharmaceutical industry and academic institution. Prior to joining Ascentage, he served as Senior Medical Director in Global Clinical Development at Novartis, responsible for BRAF/MEK project clinical strategy and clinical development. He actively led clinical projects of Tafinlar/ Mekinist in combination with immunotherapy and targeted therapies at all stages of development. Dr. Huang had also worked in Global Clinical Development as Senior Medical Director and Medical Director at GlaxoSmithKline and Bristol Myer Squibb, respectively. He played a leading role in multiple pivotal global Phase II/III trials in oncology. He contributed to the regulatory approval and life-cycle management for Erbitux, Tykerb in the US or EU, and led the global clinical development activities of brivanib in HCC. Besides the global roles, Dr. Huang had worked as Medical Advisor in Asia Pacific region at Novartis, he is responsible for the regional clinical development and medical affair activities for Glivec, Femara, Sandostain, and Afinitor. He involved in establishment of clinical research organization and updating skill levels of medical team across Asia Pacific region to enable participation in global development studies and initiation of regional and local clinical studies. Before joining industry, Dr. Huang had been an oncology research fellow at Chinese University of Hong Kong and Queen's University in Canada, he had also practiced as physician in oncology at Sun Yat-sen University Cancer Center for six years. Dr. Huang received an M.D. degree from Medical School of Sun Yat-sen University and a Master degree in Clinical Epidemiology from Queen's University in Canada. "I am thrilled to welcome Jason to join Ascentage family. He brings a wealth of knowledge and experience in oncology drug development." said Yifan Zhai, M.D., Ph.D., Chief Medical Officer of Ascentage, "Jason's leadership in clinical development and translational medicine will be instrumental for us to advance our oncology/hematology pipeline on a global basis." "I am very much impressed by Ascentage's science-driven culture and its grit in tackling the once undruggable Protein-Protein Interaction targets," said Dr. Huang. "It is more than exciting to join Ascentage as the company is emerging fast into a global biotech. I look forward to working closely with my passionate colleagues and dedicating my expertise and experience to developing transformational therapeutics for patients worldwide." Ascentage Pharma is a global, clinical-stage biopharmaceutical company, dedicated to discovery and development of "first-in-class" and "best-in-class" small-molecule targeted therapeutics for addressing unmet medical needs in cancers, hepatitis B and age-related diseases. Ascentage has world-leading proprietary Protein-Protein Interaction drug discovery technologies and holds over 100 international patents. Ascentage currently has six small molecule drugs in phase I-II trials in US, Australia and China and additional programs in preclinical stages. The established R&D pipeline of Ascentage includes the inhibitors to a number of key proteins, including IAP, Bcl-2/Bcl-x and MDM2-p53, that regulate a tumor cell's programmed cell death program; 2nd and/or 3rd generation of kinase inhibitors that overcome mutant resistance in cancer therapy; and inhibitors of epigenetics. For more information, please visit www.ascentagepharma.com.
Wang J.,Sun Yat Sen University |
Yang D.,Sun Yat Sen University |
Yang D.,Ascentage Pharma |
Luo Q.,Sun Yat Sen University |
And 8 more authors.
International Journal of Oncology | Year: 2017
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite improved remission rates, current treatment regimens for AML are often associated with a very poor prognosis and adverse effects, necessitating more effective and safer agents. B-cell leukemia/lymphoma 2 (Bcl-2) family proteins regulate apoptotic pathway that can be targeted with small molecule inhibitors. APG-1252-12A is a Bcl-2 homology (BH)-3 mimetic that specifically binds to Bcl-2 and Bcl-xl, which has shown efficacy in some Bcl-2 dependent hematological cancers. In this study, we investigated whether APG-1252-12A inhibits the growth of five leukemia cell lines in a concentration- or time-dependent manner by MTS assay. Following treatment of AML cell line HL-60 with this compound, cell apoptosis was detected using flow cytometry and nuclear condensation was observed after Hoechst 33258 dye. Immunoblotting for cytochrome c, cleaved caspase-3 and PARP-1 cleavage was used to demonstrate the mechanism of inducing mitochondria-dependent apoptosis by APG-1252-12A. Our findings showed that this new compound inhibited cell proliferation in five leukemia cell lines and induced apoptotic death. There was a link between the level of Bcl-2 protein and IC50. APG-1252-12A targeted mitochondria and induced caspase-dependent apoptosis by inducing the HL-60 cell cytochrome c released, PARP cleavage and caspase activation. These data suggested that APG-1252-12A is a candidate drug for the in vivo analysis and clinical evaluation in AML.
Chen H.,Sun Yat Sen University |
Luo D.,Sun Yat Sen University |
Zhang L.,Sun Yat Sen University |
Lin X.,Sun Yat Sen University |
And 13 more authors.
Oncotarget | Year: 2017
Dedifferentiated papillary thyroid cancer (DePTC) is characterized by aggressive growth, recurrence, distant metastasis, and resistance to radioactive iodine (RAI) therapy. DePTC is also accompanied by poor prognosis and high early-mortality. Nevertheless, most DePTC cells show intact p53 downstream functionality. In cells with wild-type p53, the murine double minute2 (MDM2) protein interacts with p53 and abrogates its activity. Inhibition of the MDM2-p53 interaction restores p53 activity and leads to cell cycle arrest and apoptosis. Restoring p53 function by inhibiting its interaction with p53 suppressors such as MDM2 is thus a promising therapeutic strategy for the treatment of DePTC. The novel MDM2-p53 interaction antagonist APG115 is an analogue of SAR405838, and is being tested in a phase I clinical trial. In this study, we evaluated the efficacy of APG115 as a single-agent to treat DePTC. APG115 diminished the viability of p53 wild-type DePTC cells and induced cell cycle arrest and apoptosis. In a human xenograft mouse model, APG115 elicited robust tumor regression and cell apoptosis. These data demonstrate that further research is warranted to determine whether APG115 can be used to effectively treat DePTC patients. © Chen et al.
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
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 | Entity website
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Ascentage Pharma | Entity website
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 | Entity website
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 ...