Le An
Genentech
5 Papers
17 Citations
Le An is an academic researcher from Genentech. The author has contributed to research in topics: Structure–activity relationship & In vivo. The author has an hindex of 5, co-authored 5 publications.
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Papers
GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP).
F. Anthony Romero,Jeremy Murray,Kwong Wah Lai,Vickie Tsui,Brian K. Albrecht,Le An,Maureen Beresini,Gladys de Leon Boenig,Sarah M. Bronner,Emily Chan,Kevin X. Chen,Zhongguo Chen,Edna F. Choo,Kyle Clagg,Kevin R Clark,Terry Crawford,Patrick Cyr,Denise E. de Almeida Nagata,Karen E. Gascoigne,Jane L. Grogan,Georgia Hatzivassiliou,Wei Huang,Thomas Hunsaker,Susan Kaufman,Stefan G. Koenig,Ruina Li,Yingjie Li,Xiaorong Liang,Jiangpeng Liao,Wenfeng Liu,Justin Ly,Jonathan Maher,Colin Masui,Mark Merchant,Yingqing Ran,Alexander M. Taylor,John S. Wai,Fei Wang,Xiaocang Wei,Dong Yu,Bing-Yan Zhu,Xiaoyu Zhu,Steven Magnuson +42 more
TL;DR: Structural-activity relationship studies coupled with further structure-based design targeting the LPF shelf, BC loop, and KAc regions allowed us to significantly increase potency and selectivity, resulting in the identification of non-CNS penetrant 19 that maintained good in vivo PK properties in multiple species.
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Individual serum bile acid profiling in rats aids in human risk assessment of drug-induced liver injury due to BSEP inhibition.
Steven Cepa,David Potter,Lisa Wong,Leah Schutt,Jacqueline M. Tarrant,Jodie Pang,Xiaolin Zhang,Roxanne Andaya,Laurent Salphati,Yingqing Ran,Le An,Ryan E. Morgan,Jonathan Maher +12 more
TL;DR: Serum bile acid profiling can potentially identify a mechanistic risk of clinical DILI that could be poorly detected by traditional toxicity endpoints, according to traditional toxicity testing.
23
Development of Potent and Selective Pyrazolopyrimidine IRAK4 Inhibitors.
Marian C. Bryan,Joy Drobnick,Alberto Gobbi,Aleksandr Kolesnikov,Yongsheng Chen,Naomi S. Rajapaksa,Chudi Ndubaku,Jianwen Feng,Willy M. Chang,Ross Francis,Christine Yu,Edna F. Choo,Kevin DeMent,Yingqing Ran,Le An,Claire Emson,Zhiyu Huang,Swathi Sujatha-Bhaskar,Hans Brightbill,Antonio G. DiPasquale,Jonathan Maher,John S. Wai,Brent S. McKenzie,Patrick J. Lupardus,Ali A. Zarrin,James R. Kiefer +25 more
TL;DR: Improved physicochemical properties allowed for progression into in vivo experiments, where lead molecules exhibited low clearance and showed target-based inhibition of IRAK4 signaling in an inflammation-mediated PK/PD mouse model.
21
Discovery of Potent Benzolactam IRAK4 Inhibitors with Robust in Vivo Activity.
Naomi S. Rajapaksa,Alberto Gobbi,Joy Drobnick,Steven Do,Aleksandr Kolesnikov,Jun Liang,Yongsheng Chen,Swathi Sujatha-Bhaskar,Zhiyu Huang,Hans Brightbill,Ross Francis,Christine Yu,Edna F. Choo,Kevin DeMent,Yingqing Ran,Le An,Claire Emson,Jonathan Maher,John S. Wai,Brent S. McKenzie,Patrick J. Lupardus,Ali A. Zarrin,James R. Kiefer,Marian C. Bryan +23 more
TL;DR: Application of a human whole blood assay to the discovery of a series of benzolactam IRAK4 inhibitors is described and potent molecule 19 is identified that achieves robust in vivo inhibition of cytokines relevant to human disease.
17
From a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors.
Jun Liang,Sharada Labadie,Birong Zhang,Daniel F. Ortwine,Snahel Patel,Maia Vinogradova,James R. Kiefer,Till Mauer,Victor S. Gehling,Jean-Christophe Harmange,Richard D. Cummings,Tommy Lai,Jiangpeng Liao,Xiaoping Zheng,Yichin Liu,Amy Gustafson,Erica Van der Porten,Weifeng Mao,Bianca M. Liederer,Gauri Deshmukh,Le An,Yingqing Ran,Marie Classon,Patrick Trojer,Peter S. Dragovich,Lesley J. Murray +25 more
TL;DR: Using structure-based design approach, 50 was identified with improved biochemical, cell potency and reduced MW and lower lipophilicity compared with the original hit, meeting the criteria for an in vivo tool compound from a new scaffold.