High throughput screen to identify small molecule modulators in a cell-based model of AML

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCATS	CANCER-15

Authors

• R.E. Jones
• C.Z. Chen
• A.D. Schimmer
• J. McKew
• W. Zheng

Abstract

Treatment for patients with Acute Myeloid Leukemia (AML) has remained largely unchanged over the past 20 years, with particularly poor prognosis for patients 60 years and older. The antimicrobial agent tigecycline has been previously shown to target human leukemia cell lines via mitochondrial translation inhibition and is currently being investigated in a clinical trial for AML patients. We performed a high throughput screen (HTS) of the National Chemical Genomics Center Pharmaceutical Collection (NPC) in a cell-based model for AML in combination with tigecycline in search of small molecules that function synergistically with tigecycline. The assay was successfully optimized and miniaturized to 1536-well format with robust and clean performance. In a primary screen with 3862 compounds, 180 hits were cherry picked and retested. The confirmational assay showed 12 compounds that acted synergistically with tigecycline, and 7 that acted antagonistically.

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