ChemPartner

Shanghai, China

ChemPartner

Shanghai, China
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Dr. Xu has more than 20 years of experience in the area of drug metabolism, pharmacokinetics and toxicology. She was one of the pioneers in developing cultured human hepatocytes as a tool to study metabolism of xenobiotics and induction of P450 isozymes. Prior to joining ChemPartner, Dr. Xu was the Head of the Center of Predictive ADMET at Sanofi/Icagen. She received her Ph.D. in Cell and Molecular Biology from Saint Louis University. Since the DMPK and Exploratory Toxicology department's inception in 2006, it has been one of the most rapidly growing business units in the company. This growth is a testament to the high-quality performance and experienced leadership by the scientific team. "DMPK is important to Chempartner and our biopharmaceutical clients with respect to drug discovery and development to meet unmet medical needs. We needed an experienced leader to maintain the quality of service that keep our clients satisfied and coming back. Dr. Xu's expertise, knowledge, and dedication make her a great fit for the team," said Dr. Wei Tang, President of ChemPartner. Dr. Tang previously served as Senior Vice President, Biology, Biologics, and DMPK and hired Dr. Xu  to lead the talented team. "ChemPartner's DMPK Exploratory Toxicology integrated service, working in unison with our Chemistry, Biologics, and Biology departments, is the best model for helping our clients to deliver their hits, leads, and candidates in a fast and high quality manner. Our goal at ChemPartner has always been to deliver high quality data to our clients and provide scientific interpretation of the data, thereby helping to solve problems through our expertise in DMPK and toxicology," said Dr. Xu. ChemPartner's DMPK and Exploratory Toxicology department consists of bioanalytical (small and large molecules, discovery, and regulated), in vitro ADME, in vivo pharmacokinetics, and toxicology (non-GLP and partnered GLP) groups. Working closely with Chemistry, Biology/Pharmacology, and Biologics, the department supports translational medicine with experience in formulation development, in vitro and in vivo PK extrapolation, PK/PD correlation, and biomarker analysis including metabolomics. Shanghai ChemPartner is a full-service life science CRO with over 15 years of pharmaceutical research experience. With a team of over 2000 experienced scientists, hundreds of western-trained pharmaceutical industry leaders, and experienced pharmaceutical executive leadership at the helm, ChemPartner is aligned and dedicated to technically and strategically accomplishing the research initiatives of pharma and biotech companies worldwide.


SAN FRANCISCO and SOUTH SAN FRANCISCO, Calif., July 13, 2017 /PRNewswire/ -- In a new collaboration, ShangPharma Innovation, Inc. (SPII) is providing funding and other support to scientists at UC San Francisco (UCSF) to accelerate the development of promising life science inventions. The partnership helps advance a major new initiative at UCSF to bridge academic research with industrial development. Part of this effort, which SPII will support, involves backing preclinical research to validate drug targets and to develop programs to discover new drugs. Drugs that UCSF and SPII determine to be promising in preclinical studies can then be readied for clinical trials to demonstrate safety and efficacy in patients. The collaboration agreement anticipates that SPII will provide several years of funding to carry out R&D in UCSF laboratories. SPII also will commit to spend additional amounts each year during the term of the collaboration to purchase Contract Research Organization (CRO) services in support of the projects being conducted by SPII and UCSF. CRO services will be provided by Shanghai ChemPartner Co. Ltd. (ChemPartner). SPII and UCSF will share in future value created through this innovative partnership. "When the proper bridges to fundamental research are built, important new medicines reach the marketplace, saving and improving lives around the world," said Walter H. Moos, PhD, CEO of SPII and adjunct professor of pharmaceutical chemistry at UCSF. "We have only just begun to scratch the surface of what's possible when academia and early-stage investors come together to advance novel discoveries. We look forward to enabling biomedical innovation across all borders and disciplines." Cathy Tralau-Stewart PhD, interim director of UCSF's Catalyst Program and adjunct associate professor of bioengineering and therapeutics at UCSF, said, "The translation of early research into novel therapeutics for patients requires a wide range of expertise and capabilities. This collaboration will give UCSF access to the broad range of expertise and services required and will enable the translation of more UCSF discoveries to product opportunities with real potential benefit for patients. This is an important collaboration and we look forward to working closely with the ShangPharma and ChemPartner teams." ShangPharma Innovation, Inc., founded in the US in 2016, facilitates and accelerates drug discovery, focusing on both therapeutics and technology platforms, and offers funding, incubator space, and other support to its ecosystem of collaborators, partners, and tenants. This includes sponsoring proof-of-concept research at major academic and medical centers, research institutes, and seed-stage start-ups, leading to industry collaborations and venture capital financing. ShangPharma Innovation and ChemPartner are affiliates and preferred partners. Services will be provided predominantly or solely by ChemPartner at their standard commercial rates. For more information, see http://www.shangpharmainnovation.com. UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospitals in San Francisco and Oakland - and other partner and affiliated hospitals and healthcare providers throughout the Bay Area. Please visit www.ucsf.edu/news. The Catalyst program, which is part of UCSF's Innovation Ventures, accelerates translation of research into products with clinical impact through funding, mentorship, and identification of resources. Catalyst aims to foster academic and industry collaborations as well as enhance education in early translational research and entrepreneurship. See http://ctsi.ucsf.edu/catalyst. Shanghai ChemPartner Co. Ltd., along with its subsidiary entities, is a leading research organization providing high-quality and cost-effective contract research services for the biopharmaceutical industry. ChemPartner offers integrated services across the drug discovery and development process to pharmaceutical and biotechnology companies worldwide. ChemPartner's dedication to life science is seen through its broad range of services, from discovery biologics, discovery chemistry, discovery biology, and preclinical development through pharmaceutical development and manufacturing services for small molecules and biologics. For more information, see http://www.chempartner.com.


SHANGHAI, July 12, 2017 /PRNewswire/ -- Shanghai ChemPartner today announced the appointment of Lilly Xu, Ph.D. as Vice President and the Head of DMPK and Exploratory Toxicology at the company headquarters in Shanghai, China. Dr. Xu has more than 20 years of experience in the area of drug metabolism, pharmacokinetics and toxicology. She was one of the pioneers in developing cultured human hepatocytes as a tool to study metabolism of xenobiotics and induction of P450 isozymes. Prior to joining ChemPartner, Dr. Xu was the Head of the Center of Predictive ADMET at Sanofi/Icagen. She received her Ph.D. in Cell and Molecular Biology from Saint Louis University. Since the DMPK and Exploratory Toxicology department's inception in 2006, it has been one of the most rapidly growing business units in the company. This growth is a testament to the high-quality performance and experienced leadership by the scientific team. "DMPK is important to Chempartner and our biopharmaceutical clients with respect to drug discovery and development to meet unmet medical needs. We needed an experienced leader to maintain the quality of service that keep our clients satisfied and coming back. Dr. Xu's expertise, knowledge, and dedication make her a great fit for the team," said Dr. Wei Tang, President of ChemPartner. Dr. Tang previously served as Senior Vice President, Biology, Biologics, and DMPK and hired Dr. Xu  to lead the talented team. "ChemPartner's DMPK Exploratory Toxicology integrated service, working in unison with our Chemistry, Biologics, and Biology departments, is the best model for helping our clients to deliver their hits, leads, and candidates in a fast and high quality manner. Our goal at ChemPartner has always been to deliver high quality data to our clients and provide scientific interpretation of the data, thereby helping to solve problems through our expertise in DMPK and toxicology," said Dr. Xu. ChemPartner's DMPK and Exploratory Toxicology department consists of bioanalytical (small and large molecules, discovery, and regulated), in vitro ADME, in vivo pharmacokinetics, and toxicology (non-GLP and partnered GLP) groups. Working closely with Chemistry, Biology/Pharmacology, and Biologics, the department supports translational medicine with experience in formulation development, in vitro and in vivo PK extrapolation, PK/PD correlation, and biomarker analysis including metabolomics. Shanghai ChemPartner is a full-service life science CRO with over 15 years of pharmaceutical research experience. With a team of over 2000 experienced scientists, hundreds of western-trained pharmaceutical industry leaders, and experienced pharmaceutical executive leadership at the helm, ChemPartner is aligned and dedicated to technically and strategically accomplishing the research initiatives of pharma and biotech companies worldwide.


The partnership helps advance a major new initiative at UCSF to bridge academic research with industrial development. Part of this effort, which SPII will support, involves backing preclinical research to validate drug targets and to develop programs to discover new drugs. Drugs that UCSF and SPII determine to be promising in preclinical studies can then be readied for clinical trials to demonstrate safety and efficacy in patients. The collaboration agreement anticipates that SPII will provide several years of funding to carry out R&D in UCSF laboratories. SPII also will commit to spend additional amounts each year during the term of the collaboration to purchase Contract Research Organization (CRO) services in support of the projects being conducted by SPII and UCSF. CRO services will be provided by Shanghai ChemPartner Co. Ltd. (ChemPartner). SPII and UCSF will share in future value created through this innovative partnership. "When the proper bridges to fundamental research are built, important new medicines reach the marketplace, saving and improving lives around the world," said Walter H. Moos, PhD, CEO of SPII and adjunct professor of pharmaceutical chemistry at UCSF. "We have only just begun to scratch the surface of what's possible when academia and early-stage investors come together to advance novel discoveries. We look forward to enabling biomedical innovation across all borders and disciplines." Cathy Tralau-Stewart PhD, interim director of UCSF's Catalyst Program and adjunct associate professor of bioengineering and therapeutics at UCSF, said, "The translation of early research into novel therapeutics for patients requires a wide range of expertise and capabilities. This collaboration will give UCSF access to the broad range of expertise and services required and will enable the translation of more UCSF discoveries to product opportunities with real potential benefit for patients. This is an important collaboration and we look forward to working closely with the ShangPharma and ChemPartner teams." ShangPharma Innovation, Inc., founded in the US in 2016, facilitates and accelerates drug discovery, focusing on both therapeutics and technology platforms, and offers funding, incubator space, and other support to its ecosystem of collaborators, partners, and tenants. This includes sponsoring proof-of-concept research at major academic and medical centers, research institutes, and seed-stage start-ups, leading to industry collaborations and venture capital financing. ShangPharma Innovation and ChemPartner are affiliates and preferred partners. Services will be provided predominantly or solely by ChemPartner at their standard commercial rates. For more information, see http://www.shangpharmainnovation.com. UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospitals in San Francisco and Oakland - and other partner and affiliated hospitals and healthcare providers throughout the Bay Area. Please visit www.ucsf.edu/news. The Catalyst program, which is part of UCSF's Innovation Ventures, accelerates translation of research into products with clinical impact through funding, mentorship, and identification of resources. Catalyst aims to foster academic and industry collaborations as well as enhance education in early translational research and entrepreneurship. See http://ctsi.ucsf.edu/catalyst. Shanghai ChemPartner Co. Ltd., along with its subsidiary entities, is a leading research organization providing high-quality and cost-effective contract research services for the biopharmaceutical industry. ChemPartner offers integrated services across the drug discovery and development process to pharmaceutical and biotechnology companies worldwide. ChemPartner's dedication to life science is seen through its broad range of services, from discovery biologics, discovery chemistry, discovery biology, and preclinical development through pharmaceutical development and manufacturing services for small molecules and biologics. For more information, see http://www.chempartner.com.


SPII facilitates and accelerates drug discovery by offering funding, incubator space, and other essential support to its collaborators. The partnership with TSRI marks a major new initiative for SPII to enable its mission to support therapeutic research at the earliest stages with the ultimate goal of getting innovative new treatments to patients. Under the terms of the collaboration, institute scientists will put forth translational research projects to a joint committee comprising drug discovery experts across TSRI, Calibr, and SPII.  In turn, SPII will contribute cash and in-kind services totaling up to $15 million over an initial term of three years. TSRI and Calibr will retain control over assets resulting from the collaboration, with SPII receiving a significant share of future value. "We are delighted to partner with an experienced group that has complementary infrastructure and resources," said Peter G. Schultz, Ph.D., President of TSRI and Calibr. "This new initiative allows us to further accelerate our mission of creating new medicines for unmet needs in a nimble partnership structure designed to mature the programs before out-licensing, creating significant value for patients as well as for the institute." "Biomedical R&D is one of the most challenging areas of science across all disciplines and industries. Strategic partnerships often drive success in making the impossible possible. That is exactly what we plan to do in this alliance with TSRI and Calibr," stated Walter H. Moos, Ph.D., CEO of SPII. "Unlocking the potential of top investigators at TSRI and Calibr to advance novel therapies and ultimately to save and improve lives is our joint goal." The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists - including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine - work toward their next discoveries. The institute's graduate program, which awards doctoral degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu/. ShangPharma Innovation Inc., founded in the US in 2016, facilitates and accelerates drug discovery, focusing on both therapeutics and technology platforms, and offers funding, incubator space, and other support to its ecosystem of collaborators, partners, and tenants. This includes sponsoring proof-of-concept research at academic and major medical centers, research institutes, and seed-stage start-ups, leading to industry collaborations and venture capital financing. ShangPharma Innovation and ChemPartner are affiliates and preferred partners. Services will be provided predominantly or solely by ChemPartner at their standard commercial rates. Shanghai ChemPartner Co. Ltd., along with its subsidiary entities, is a leading research organization providing high-quality and cost-effective contract research services for the biopharmaceutical industry. ChemPartner offers integrated services across the drug discovery and development process to pharmaceutical and biotechnology companies worldwide. ChemPartner's dedication to life science is seen through its broad range of services, from discovery biologics, discovery chemistry, discovery biology, and preclinical development through pharmaceutical development and manufacturing services for small molecules and biologics. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/the-scripps-research-institute-and-shangpharma-innovation-announce-translational-research-collaboration-300470942.html


- World-class research institute and new innovation center partner to accelerate early translational research - LA JOLLA, Calif., June 8, 2017 /PRNewswire/ -- The Scripps Research Institute (TSRI) and ShangPharma Innovation, Inc. (SPII) today announced a strategic collaboration to accelerate the development of innovative drug candidates through scientific collaboration, a services relationship with Shanghai ChemPartner Co. Ltd. (ChemPartner), and sponsored research at TSRI and its drug discovery affiliate, California Institute for Biomedical Research (Calibr). The parties aim to leverage the drug discovery pipeline, expertise, and momentum emerging from the TSRI and Calibr affiliation announced late last year. SPII facilitates and accelerates drug discovery by offering funding, incubator space, and other essential support to its collaborators. The partnership with TSRI marks a major new initiative for SPII to enable its mission to support therapeutic research at the earliest stages with the ultimate goal of getting innovative new treatments to patients. Under the terms of the collaboration, institute scientists will put forth translational research projects to a joint committee comprising drug discovery experts across TSRI, Calibr, and SPII.  In turn, SPII will contribute cash and in-kind services totaling up to $15 million over an initial term of three years. TSRI and Calibr will retain control over assets resulting from the collaboration, with SPII receiving a significant share of future value. "We are delighted to partner with an experienced group that has complementary infrastructure and resources," said Peter G. Schultz, Ph.D., President of TSRI and Calibr. "This new initiative allows us to further accelerate our mission of creating new medicines for unmet needs in a nimble partnership structure designed to mature the programs before out-licensing, creating significant value for patients as well as for the institute." "Biomedical R&D is one of the most challenging areas of science across all disciplines and industries. Strategic partnerships often drive success in making the impossible possible. That is exactly what we plan to do in this alliance with TSRI and Calibr," stated Walter H. Moos, Ph.D., CEO of SPII. "Unlocking the potential of top investigators at TSRI and Calibr to advance novel therapies and ultimately to save and improve lives is our joint goal." The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists - including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine - work toward their next discoveries. The institute's graduate program, which awards doctoral degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu/. ShangPharma Innovation Inc., founded in the US in 2016, facilitates and accelerates drug discovery, focusing on both therapeutics and technology platforms, and offers funding, incubator space, and other support to its ecosystem of collaborators, partners, and tenants. This includes sponsoring proof-of-concept research at academic and major medical centers, research institutes, and seed-stage start-ups, leading to industry collaborations and venture capital financing. ShangPharma Innovation and ChemPartner are affiliates and preferred partners. Services will be provided predominantly or solely by ChemPartner at their standard commercial rates. Shanghai ChemPartner Co. Ltd., along with its subsidiary entities, is a leading research organization providing high-quality and cost-effective contract research services for the biopharmaceutical industry. ChemPartner offers integrated services across the drug discovery and development process to pharmaceutical and biotechnology companies worldwide. ChemPartner's dedication to life science is seen through its broad range of services, from discovery biologics, discovery chemistry, discovery biology, and preclinical development through pharmaceutical development and manufacturing services for small molecules and biologics. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/the-scripps-research-institute-and-shangpharma-innovation-announce-translational-research-collaboration-300470942.html


Zeng X.,Shanghai University | Lin Y.,Shanghai University | Yin C.,Shanghai University | Zhang X.,Chinese National Human Genome Center at Shanghai | And 7 more authors.
Hepatology | Year: 2011

Hepatocyte nuclear factor-1alpha (HNF1α) is one of the key transcription factors of the HNF family, which plays a critical role in hepatocyte differentiation. Substantial evidence has suggested that down-regulation of HNF1α may contribute to the development of hepatocellular carcinoma (HCC). Herein, human cancer cells and tumor-associated fibroblasts (TAFs) were isolated from human HCC tissues, respectively. A recombinant adenovirus carrying the HNF1α gene (AdHNF1α) was constructed to determine its effect on HCC in vitro and in vivo. Our results demonstrated that HCC cells and HCC tissues revealed reduced expression of HNF1α. Forced reexpression of HNF1α significantly suppressed the proliferation of HCC cells and TAFs and inhibited the clonogenic growth of hepatoma cells in vitro. In parallel, HNF1α overexpression reestablished the expression of certain liver-specific genes and microRNA 192 and 194 levels, with a resultant increase in p21 levels and induction of G 2/M arrest. Additionally, AdHNF1α inhibited the expression of cluster of differentiation 133 and epithelial cell adhesion molecule and the signal pathways of the mammalian target of rapamycin and transforming growth factor beta/Smads. Furthermore, HNF1α abolished the tumorigenicity of hepatoma cells in vivo. Most interestingly, intratumoral injection of AdHNF1α significantly inhibited the growth of subcutaneous HCC xenografts in nude mice. Systemic delivery of AdHNF1α could eradicate the orthotopic liver HCC nodules in nonobese diabetic/severe combined immunodeficiency mice. Conclusion: These results suggest that the potent inhibitive effect of HNF1α on HCC is attained by inducing the differentiation of hepatoma cells into mature hepatocytes and G 2/M arrest. HNF1α might represent a novel, promising therapeutic agent for human HCC treatment. Our findings also encourage the evaluation of differentiation therapy for tumors of organs other than liver using their corresponding differentiation-determining transcription factor. (HEPATOLOGY 2011) © 2011 American Association for the Study of Liver Diseases.


SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Circle Pharma, Inc. today announced a Series A financing round in which it has issued over $4.5M of shares of Series A Preferred Stock. The financing was led by Mission Bay Capital, with Pfizer Inc. (NYSE:PFE), ShangPharma Investment Group, Ltd. and a syndicated group of individual investors joining the round. In connection with the financing, Walter H. Moos, Ph.D., representing ShangPharma, has joined the Circle Board of Directors. “We are delighted with the participation of such high caliber investors in our first equity round,” said David J. Earp, J.D., Ph.D., Circle’s president and CEO. “With our seed funding, we established Circle’s computational design platform, advanced our synthetic chemistry capabilities in collaboration with ChemPartner, and engaged in a target-based collaboration with Pfizer. The Series A funds will be used to support Circle’s therapeutic pipeline, which is focused on intracellular protein-protein interactions that are key drivers in oncogenic pathways. We are also now building a physical library of cell-permeable macrocycles to augment our computational design tools, and this library will later be available to our collaboration partners. We are particularly excited to welcome Walter Moos to our Board of Directors. Dr. Moos brings a wealth of life sciences R&D experience, having served most recently as the president of SRI Biosciences and previously in senior executive roles at MitoKor, Chiron and Warner-Lambert/Parke-Davis. His teams have advanced numerous pharmaceutical products from discovery to commercialization, and we are fortunate to have him join Circle.” “I am very much looking forward to taking an active role on Circle’s board,” said Walter Moos. “The combination of innovative technology and the great team at Circle could help unlock high value targets that have long been considered out of reach of drug developers.” Dr. Moos has served on about 20 business and scientific boards, including Amunix, Oncologic (Aduro), Onyx (Amgen), Rigel and the Biotechnology Industry Organization (BIO). Macrocyclic peptides have the potential to allow drug developers to address the large proportion of known therapeutic targets (estimated at up to 80%) that are considered undruggable with conventional small molecule or biologic modalities. In particular, there is great interest in developing macrocycles to modulate protein-protein interactions, which play a role in almost all disease conditions, including cancer, fibrosis, inflammation and infection. However, the development of macrocyclic therapeutics has been limited by the need for a greater understanding of how to develop macrocycles with appropriate pharmacokinetics, cell permeability and oral bioavailability. Circle’s ability to design potent macrocycles with intrinsic cell permeability could unlock access to challenging, high value therapeutic targets that have been out of reach to other approaches. Circle is developing a new paradigm for macrocycle drug discovery based on rational design and synthetic chemistry. Circle’s technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by oral administration. Circle’s macrocycle development platform is applicable across a wide range of serious diseases; the company is initially focusing its internal development efforts on intracellular protein-protein interactions that are key drivers in cancer. Circle’s founders are Prof. Matthew P. Jacobson (Chair of the Dept. of Pharmaceutical Chemistry at UC San Francisco and co-founder of Global Blood Therapeutics (NASDAQ: GBT) and Relay Therapeutics) and Prof. R. Scott Lokey (Dept. of Chemistry and Biochemistry, UC Santa Cruz and director of the UCSC Chemical Screening Center).


Delabarre B.,Agios Pharmaceuticals | Gross S.,Agios Pharmaceuticals | Fang C.,ChemPartner | Gao Y.,ChemPartner | And 5 more authors.
Biochemistry | Year: 2011

Glutaminase (GLS1/2) catalyzes the conversion of l-glutamine to l-glutamate and ammonia. The level of a splice variant of GLS1 (GAC) is elevated in certain cancers, and GAC is specifically inhibited by bis-2-(5-phenylacetimido-1,2,4, thiadiazol-2-yl)ethyl sulfide (BPTES). We report here the first full-length crystal structure of GAC in the presence and absence of BPTES molecules. Two BPTES molecules bind at an interface region of the GAC tetramer in a manner that appears to lock the GAC tetramer into a nonproductive conformation. The importance of these loops with regard to overall enzymatic activity of the tetramer was revealed by a series of GAC point mutants designed to create a BPTES resistant GAC. © 2011 American Chemical Society.


Cheng Y.,Georgia State University | Ni N.,Georgia State University | Yang W.,ChemPartner | Wang B.,Georgia State University
Chemistry - A European Journal | Year: 2010

The boronic acid group is an important recognition moiety for sensor design. Herein, we report a series of isoquinolinylboronic acids that have extraordinarily high affinities for diol-containing compounds at physiological pH. In addition, 5- and 8-isoquinolinylboronic acids also showed fairly high binding affinities towards D-glucose (Ka=42 and 46M-1, respectively). For the first time, weak but encouraging binding of cis-cyclohexanediol was found for these boronic acids. Such binding was coupled with significant fluorescence changes. Furthermore, 4- and 6- isoquinolinylboronic acids also showed the ability to complex methyl α-D-glucopyranose (Ka=3 and 2M-1, respectively). Be the first! The diol-binding behavior of a series of isoquinolinylboronic acids was investigated by monitoring the changes of their fluorescence intensity (see figure for an example, 6-IQBA=6-isoquinolinylboronic acid). For the first time, a boronic acid derivative that binds cis-cyclohexanediol was identified. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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