Rebecca Turincio

Genentech

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

John C. Chabala

Nexgenix Pharmaceuticals (United States)

Yan Lee

Seoul National University

Roman Sakowicz

Gilead Sciences (United States)

Alex Fritsch

Cytokinetics (United States)

Paul Gonzales

Translational Genomics Research Institute

Anne Crompton

The Rotherham NHS Foundation Trust

Jeffrey T. Finer

Cytokinetics (United States)

Steve Weitman

The University of Texas Health Science Center at San Antonio

Robert V. Moody

University of Victoria

Kenneth W. Wood

Frontier Science & Technology Research Foundation

Cooperative Institutions

Genentech

Cytokinetics (United States)

Roche (United States)

Gilead Sciences (United States)

Harvard University

University of California, San Francisco

Toxicologie, Pharmacologie et Signalisation Cellulaire

Massachusetts Institute of Technology

University of Edinburgh

GlaxoSmithKline (United States)

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Legends to Supplementary Figures from Antitumor Activity of a Kinesin Inhibitor

Roman Sakowicz Jeffrey T. Finer Christophe Béraud Anne Crompton Evan Lewis

Legends to Supplementary Figures from Antitumor Activity of a Kinesin Inhibitor

Kinesin

10.1158/0008-5472.22363722

Cite

Citations (0)

High throughput screening identifies novel, cell cycle‐arresting small molecule enhancers of transient protein expression

Biotechnology Progress (2017)

Hermann‐Josef Meyer Rebecca Turincio Shirley Ng Juan Li Blair Wilson

Transient gene expression in mammalian cells is an efficient process for producing recombinant proteins for various research applications to support large molecule therapeutics development. For the first time, we report a high throughput small molecule (SM) screen to identify novel compounds that increase antibody titers after polyethylenimine (PEI) transient transfection of a HEK293 cell line. After screening 31,413 SMs in a 50 μL scaled-down process, we validated 164 SMs to improve yields by up to twofold. The titer increase mediated by the SMs varied for different antibodies. SM dose optimizations resulted in almost threefold higher titers. The top 2, structurally distinct SM hits, increased antibody titers more than twofold in a 1 mL production process. Averaged across three antibodies of different expression levels, the compounds enhanced transient productivity by ∼80%. Intriguingly, both compounds arrested cells in the G2/M cell cycle phase leading to a decrease in growth and nutrient consumption, while elevating titer, nuclear plasmid DNA (pDNA) copy numbers, and mRNA levels. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 3:1579-1588, 2017.

Transient (computer programming)

High-Throughput Screening

10.1002/btpr.2517

Cite

Citations (9)

Supplementary Fig. 2 from Antitumor Activity of a Kinesin Inhibitor

Roman Sakowicz Jeffrey T. Finer Christophe Béraud Anne Crompton Evan Lewis

Supplementary Fig. 2 from Antitumor Activity of a Kinesin Inhibitor

Kinesin

10.1158/0008-5472.22363716.v1

Cite

Citations (0)

Supplementary Fig. 3 from Antitumor Activity of a Kinesin Inhibitor

Roman Sakowicz Jeffrey T. Finer Christophe Béraud Anne Crompton Evan Lewis

Supplementary Fig. 3 from Antitumor Activity of a Kinesin Inhibitor

Kinesin

10.1158/0008-5472.22363713

Cite

Citations (0)

Small-Molecule Library Subset Screening as an Aid for Accelerating Lead Identification

SLAS DISCOVERY (2014)

Maureen H. Beresini Yichin Liu Timothy D. Dawes Kevin Clark Linda Orren

Several small-compound library subsets (14,000 to 56,000) have been established to complement screening of a larger Genentech corporate library (~1,300,000). Two validation sets (~1% of the total library) containing compounds representative of the main library were chosen by selection of plates or individual compounds. Use of these subsets guided selection of assay configuration, validated assay reproducibility, and provided estimates of hit rates expected from our full library. A larger diversity subset representing the scaffold diversity of the full library (3.4% of the total) was designed for screening more challenging targets with limited reagent availability or low-throughput assays. Retrospective analysis of this subset showed hit rates similar to those of the main library while recovering a higher proportion of hit scaffolds. Finally, a property-restricted diversity set called the "in-between library" was established to identify ligand-efficient compounds of molecular size between those typically found in fragment and high-throughput screening libraries. It was screened at fivefold higher concentrations than the main library to facilitate identification of less potent yet ligand-efficient compounds. Taken together, this work underscores the value of generating multiple purpose-focused, diversity-based library subsets that are designed using computational approaches coupled with internal screening data analyses to accelerate the lead discovery process.

High-Throughput Screening

Chemical library

Identification

10.1177/1087057114522515

Cite

Citations (18)

Legends to Supplementary Figures from Antitumor Activity of a Kinesin Inhibitor

Roman Sakowicz Jeffrey T. Finer Christophe Béraud Anne Crompton Evan Lewis

Legends to Supplementary Figures from Antitumor Activity of a Kinesin Inhibitor

Kinesin

10.1158/0008-5472.22363722.v1

Cite

Citations (0)

Data from Antitumor Activity of a Kinesin Inhibitor

Roman Sakowicz Jeffrey T. Finer Christophe Béraud Anne Crompton Evan Lewis

<div>Abstract<p>Several members of the kinesin family of microtubule motor proteins play essential roles in mitotic spindle function and are potential targets for the discovery of novel antimitotic cancer therapies. KSP, also known as <i>Hs</i>Eg5, is a kinesin that plays an essential role in formation of a bipolar mitotic spindle and is required for cell cycle progression through mitosis. We identified a potent inhibitor of KSP, CK0106023, which causes mitotic arrest and growth inhibition in several human tumor cell lines. Here we show that CK0106023 is an allosteric inhibitor of KSP motor domain ATPase with a <i>K</i><sub>i</sub> of 12 nm. Among five kinesins tested, CK0106023 was specific for KSP. In tumor-bearing mice, CK0106023 exhibited antitumor activity comparable to or exceeding that of paclitaxel and caused the formation of monopolar mitotic figures identical to those produced in cultured cells. KSP was most abundant in proliferating human tissues and was absent from cultured postmitotic neurons. These findings are the first to demonstrate the feasibility of targeting mitotic kinesins for the treatment of cancer.</p></div>

Kinesin

Antimitotic Agent

10.1158/0008-5472.c.6493848.v1

Cite

Citations (0)

Supplementary Fig. 3 from Antitumor Activity of a Kinesin Inhibitor

Roman Sakowicz Jeffrey T. Finer Christophe Béraud Anne Crompton Evan Lewis

Supplementary Fig. 3 from Antitumor Activity of a Kinesin Inhibitor

Kinesin

10.1158/0008-5472.22363713.v1

Cite

Citations (0)