Figure Legends (S1-S5) from The Anticancer Activity of a First-in-class Small-molecule Targeting PCNA
Year: 2023
Type: other
Abstract: Figure Legends Supplemental figure legend: Figure S1. A diagram illustrating the process of virtual screen and follow-up cellular assays used in compound triage. The virtual screen by the computer modeling programs, MOE and Glide, is based on the known crystal structures of the PCNA/FEN1 complex that are available from the RCSB protein database. The cellular assays that led to the identification of AOH39 is described in Figure S3. Figure S2. The chemical structures of the 57 hits (AOH compounds) identified by the virtual screen. Compounds sharing structural similarities are organized on the same rows. Compounds that showed inhibitory activities on cancer cells are highlighted. Figure S3. Effect of AOH compounds on cell growth. The SK-N-AS and SK-N-DZ NB cells and human PBMCs were incubated in the presence of various concentrations of the indicated AOH compounds for 72 hours. The cell growth was measured by a CellTiter-Glo assay (Promega, Madison, WI). The relative cell abundance was graphed by Prism. Figure S4. Effect of AOH1160 on NCI60 cancer cells. AOH1160 was submitted to the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI). The compound was tested in the NCI60 cell lines in the standard 5-dose assay as described (https://dtp.cancer.gov/discovery_development/nci-60/methodology.htm). Briefly, cells were incubated in the presence of various concentrations of AOH1160 for 48 hours. Cells growth was analyzed by a Sulforhodamine B (SRB) assay after cells were fixed by ice-cold 10% trichloroacetic acid (TCA). The GI50 in molar for each cell line was calculated by DTP. Shown in the graph are the LogGI50. Figure S5. Enhanced sensitivity to cisplatin by AOH1160. Human SK-N-AS NB cells were treated with or without 1 ï�M of cisplatin (CPT) in the presence or absence of 500 nM of AOH1160 for 18 h. Cells were washed with growth medium and were cultured in fresh media for 3 weeks to allow colony formation. The normalized colony counts under each treatment condition in triplicates were averaged and graphed plus/minus standard deviations. Based on Bliss independence model (see Methods), the combination index (Cl) for 1 ï�M of CPT and 500 nM of AOH1160 is about 0.74.
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
OpenAlex ID: W4361887393