Affiliation: Genentech Inc
- Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell lineYichin Liu
Center for Neurologic Diseases, Brigham and Women s Hospital, 65 Landsdowne Street, Cambridge, MA 02139, USA
Chem Biol 10:837-46. 2003..The molecular mechanism of this response remains to be determined...
- High-throughput assays for sirtuin enzymes: a microfluidic mobility shift assay and a bioluminescence assayYichin Liu
Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
Anal Biochem 378:53-9. 2008..Kinetic parameters of peptide and NAD(+) cosubstrates and IC(50) values of standard reference inhibitors determined in either assay were similar. With robust Z' values (0.7), both assays are amenable to high-throughput screening...
- A therapeutic antibody targeting BACE1 inhibits amyloid-β production in vivoJasvinder K Atwal
Neurodegeneration Labs, Department of Neuroscience, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
Sci Transl Med 3:84ra43. 2011..Nevertheless, therapeutic success with anti-BACE1 will depend on improving antibody uptake into the brain...
- Case studies of minimizing nonspecific inhibitors in HTS campaigns that use assay-ready platesYichin Liu
Biochemical Pharmacology and Early Leads, Genentech, Inc, South San Francisco, CA 90480, USA
J Biomol Screen 17:225-36. 2012..These case studies support a model where a diversity set of compounds should be tested first for hit rates as a function of order of addition, carrier protein, and relevant mechanistic studies prior to launch of the HTS campaign...
- Identification of 2-amino-5-aryl-pyrazines as inhibitors of human lactate dehydrogenaseBenjamin P Fauber
Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA Electronic address
Bioorg Med Chem Lett 23:5533-9. 2013..A crystal structure of an improved compound bound to human LDHA was also obtained and it explained many of the observed structure-activity relationships. ..
- Purification and kinetic characterization of human indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) and discovery of selective IDO1 inhibitorsDavid Meininger
Protein Sciences, Amgen Inc, Seattle, WA 98119, USA
Biochim Biophys Acta 1814:1947-54. 2011..Docking of Amg-1 and related analogs to the known structure of IDO1 and to homology-modeled IDO2 suggests possible rationales for the different inhibition profiles of IDO1 and IDO2...
- Identification of substituted 2-thio-6-oxo-1,6-dihydropyrimidines as inhibitors of human lactate dehydrogenasePeter S Dragovich
Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
Bioorg Med Chem Lett 23:3186-94. 2013..48 μM). A crystal structure of an optimized compound bound to human LDHA was obtained and explained many of the observed structure-activity relationships...
- Structural and biochemical analyses of the catalysis and potency impact of inhibitor phosphoribosylation by human nicotinamide phosphoribosyltransferaseAngela Oh
Genentech, Inc, Department of Structural Biology, 1 DNA Way, South San Francisco, California 94080 USA
Chembiochem 15:1121-30. 2014..Our data support a model for cellularly active NAMPT inhibitors that undergo NAMPT-catalyzed phosphoribosylation to produce pRib adducts that retain efficient binding to the enzyme. ..
- Label-free high-throughput assays to screen and characterize novel lactate dehydrogenase inhibitorsErica Vanderporten
Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA 94080, USA
Anal Biochem 441:115-22. 2013..7, these two high-throughput assays for LDH are both label free and complementary to each other in the HTS workflow by monitoring the activities of the compounds on each half of the LDH redox reaction...
- Assessment of the integrity of compounds stored in assay-ready plates using a kinase sentinel assayAda Chen
Therapeutic Discovery, Amgen, Inc, 1120 Veterans Blvd, South San Francisco, CA 94080 USA
Comb Chem High Throughput Screen 16:644-51. 2013....
- Differential effects of divalent manganese and magnesium on the kinase activity of leucine-rich repeat kinase 2 (LRRK2)Brian Lovitt
Biochemical Pharmacology and Early Leads, Genentech, Inc, One DNA Way, South San Francisco, California 90480, USA
Biochemistry 49:3092-100. 2010....
- Allosteric inhibition of BACE1 by an exosite-binding antibodyWeiru Wang
Department of Structural Biology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, United States Electronic address
Curr Opin Struct Biol 23:797-805. 2013..This binding mode, along with the enzymatic inhibition pattern, suggests that anti-BACE1 functions through an allosteric inhibition mechanism. ..
- Discovery of selective LRRK2 inhibitors guided by computational analysis and molecular modelingHuifen Chen
Discovery Chemistry Department, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, United States
J Med Chem 55:5536-45. 2012....
- Discovery of acetyl-coenzyme A carboxylase 2 inhibitors: comparison of a fluorescence intensity-based phosphate assay and a fluorescence polarization-based ADP Assay for high-throughput screeningYichin Liu
Amgen Inc, Thousand Oaks, CA 91320 1799, USA
Assay Drug Dev Technol 5:225-35. 2007..Acetyl-coenzyme A carboxylase inhibitors were identified by these high-throughput screening methods and were confirmed in a radiometric high performance liquid chromatography assay of malonyl-coenzyme A production...