Syk, a non-receptor type of tyrosine kinase, plays a pivotal role in the regulation of the B-cell receptor (BCR) signaling pathway, which regulates proliferation, differentiation and survival of B lymphocytes.The abnormal activation of BCR signaling is closely related to transformation and development of B-cell lymphoma. HMPL-523, a Novel Syk Inhibitor, Showed Anti-Tumor Activities in Vitro and in Vivo Authors: Na Yang, Wei Deng, Qiaoling Sun, Junqing Liang, Linfang Wang, Shiming Fan, Renxiang Tang, Ying Yu, Junen Sun, Feng Zhou, Guangxiu Dai, Weiguo Qing, Weiguo Su and Yongxin Ren 605. Molecular Pharmacology, Drug Resistance-Lymphoid and Other Diseases Monday, December 5, 2016, 6:00PM – 8:00PM (PST) The presentation is available at www.chi-med.com/wp-content/uploads/2016/12/pre161206_523ash.pdf . Potent anti-tumor activity and combination synergy with other therapies In vitro in B-cell lymphoma cell lines with Syk/BCR dysregulation, HMPL-523 was found to block phosphorylation of B-cell linker protein as well as inhibit cell viability by inhibiting cell survival and increasing apoptotic rate.HMPL-523 also showed synergistic anti-tumor activity on human diffused large B-cell lymphoma cells, in combination with other drugs such as Phosphoinositide-3-Kinase inhibitors, B-cell lymphoma 2 family inhibitors, or chemotherapies.Potent anti-tumor activity was also demonstrated in nude mice bearing B-cell lymphoma xenograft tumors with Syk/BCR dysregulation. Clinical development in oncology and immunology In hematological malignancies, HMPL-523 is currently being studied in a Phase I dose escalation study, which was initiated in Australia in January 2016 and is expected to complete in the first half of 2017.This study is in patients with relapsed and/or refractory B-cell non-Hodgkin’s lymphoma or chronic lymphocytic leukemia for whom there is no standard therapy. HMPL-523 is also being studied in immunological indications.Clinical data for HMPL-523 in a Phase I dose-escalating study in healthy volunteers in Australia was recently presented at the 2016 Annual Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals, which was held in November 2016.The detailed poster presentation can be viewed at www.chi-med.com/wp-content/uploads/2016/11/pre1611141.png . The Company plans to initiate a Phase II study in the U.S. in 2017. About the ASH Annual Meeting The ASH annual meeting, a scientific conference focused on malignant and non-malignant hematology, brings together more than 20,000 hematology professionals from around the world.The meeting provides an educational experience, with thousands of scientific abstracts highlighting the latest research in the field available for review, as well as the opportunity to network with a global community of professionals from every subspecialty. About B-cell signaling The BCR signaling pathway regulates proliferation, differentiation and survival of B lymphocytes, a major cellular component of the immune system.The abnormal activation of BCR signaling is closely related to transformation and development of hematological cancers (i.e. B-cell malignancies) including lymphoma and leukemia, as well as autoimmune diseases, such as rheumatoid arthritis.Targeted B-cell receptor signaling therapies, including monoclonal antibodies and small molecules, have been proven to be clinically effective for the treatment of B-cell malignancies, leading to scientific and commercial success. Syk is a key protein involved in the B-cell signaling pathway.
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Houston Astros Chris Devenski pitches against the Chicago Cubs during the sixth inning at Minute Maid Park Saturday, Sept. 10, 2016, in Houston. Photo: Melissa Phillip, Houston Chronicle Astros plan for Chris Devenski to begin spring training as a starter 1/4 Back to Gallery NATIONAL HARBOR, Md. — The Astros plan to stretch out Chris Devenski as a starter in spring training before deciding whether to include him in their rotation or utilize him in relief. Manager A.J. Hinch indicated on Tuesday the team will build the 26-year-old righthander up to at least three or four innings in Grapefruit League games. A determination on the pitcher’s role to begin 2017 wouldn’t be required until the final few weeks of spring training. medical school interview prepDevenski, who finished fourth in 2016 American League rookie of the year voting, posted a 1.61 ERA in 83 2/3 innings of relief but a 4.01 ERA in 24 2/3 innings spanning five starts. Four of his starts came in late April or early May, before the development of his slider gave him a reliable third pitch to complement his fastball-changeup combination. “Devenski’s going to have value for us one way or another, and he’s going to be a multi-inning pitcher one way or another,” Astros general manager Jeff Luhnow said.
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