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Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors.

Abstract：

:Therapeutic development of a targeted agent involves a series of decisions over additional activities that may be ignored, eliminated or pursued. This paper details the concurrent application of two methods that provide a spectrum of information about the biological activity of a compound: biochemical profiling on a large panel of kinase assays and transcriptional profiling of mRNA responses. Our mRNA profiling studies used a full dose range, identifying subsets of transcriptional responses with differing EC(50)s which may reflect distinct targets. Profiling data allowed prioritization for validation in xenograft models, generated testable hypotheses for active compounds, and informed decisions on the general utility of the series.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Ross-Macdonald P,de Silva H,Patel V,Truong A,He A,Neuhaus I,Tilford C,Ji R,Siemers N,Greer A,Carboni J,Gottardis M,Menard K,Lee F,Dodier M,Frennesson D,Sampognaro A,Saulnier M,Trainor G,Vyas D,Zimmermann K,Wittm

doi

10.1016/j.bmc.2011.10.090

subject

Has Abstract

pub_date

2012-03-15 00:00:00

pages

1961-72

issue

6

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)00917-5

journal_volume

20

pub_type

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