AID	Name	Type	Comment
2386	Probe Development Summary for Inhibitors of Bloom's syndrome helicase (BLM)	summary	Summary AIS

Survival of cells and the faithful propagation of the genome depend on elaborate mechanisms of detecting and repairing DNA damage. Treatment of advanced cancer relies on radiation therapy or chemotherapy, which kill cancer cells by causing extensive DNA damage. It is often found, that cancer cells develop resistance to therapy through enhanced activity of DNA repair functions; this has led to an increased interest in developing drugs that interfere with DNA repair, which could sensitize cancer cells to conventional therapy. Bloom syndrome helicase (BLM), is important in resolving abnormal DNA structures formed during replication or homologous recombination. Shutting down the expression of BLM leads to chromosomal instability and higher radiation sensitivity in cultured cells.


This bioassay provides profiling data on aqueous kinetic solubility (PBS @ pH 7.4) of one of the lead compounds developed in the APE1 inhibitors project.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Production Centers Network [MLPCN]

MLSCN Grant: MH087284
PI Name: Dr. Opher Gileadi, Structural Genomics Consortium, University of Oxford, UK

1. 8ul of reference and test compound stock solution were added to 392ul 100mM phosphate buffer (pH 7.4)

2. Sample tubes were shaken for 1 hr (1000 rpm) at room temperature

3. Samples were centrifuged (10 min at 12000 rpm) to precipitate un-dissolved particles

4. Supernatants were transferred to new tubes

5. Concentration of the supernatant was determined by LC-UV or LC-MS/MS

Compounds are "active" if solubility is greater than 20; "inconclusive" if solubility is between 10 and 20; "inactive" if solubility is less than 10.

PUBCHEM_ACTIVITY_SCORE is the solubility rounded to the closet whole number.

Grant Number: MH087284