Skip to main content

Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening.

Publication ,  Journal Article
Choi, HW; Chan, C; Shterev, ID; Lynch, HE; Robinette, TJ; Johnson-Weaver, BT; Shi, J; Sempowski, GD; Kim, SY; Dickson, JK; Gooden, DM ...
Published in: SLAS Discov
July 2019

Mast cells (MCs) are known to regulate innate and adaptive immunity. MC activators have recently been described as safe and effective vaccine adjuvants. Many currently known MC activators are inadequate for in vivo applications, however, and research on identifying novel MC activators is limited. In this study, we identified novel MC activators by using high-throughput screening (HTS) assays using approximately 55,000 small molecules. Data sets obtained by the primary HTS assays were statistically evaluated using quality control rules and the B-score calculation, and compounds with B-scores of >3.0 were chosen as mast cell activators (hits). These hits were re-evaluated with secondary and tertiary HTS assays, followed by further statistical analysis. From these hits, we selected 15 compounds that caused degranulation in murine and human MCs, with potential for flexible chemical modification for further study. Among these 15 compounds, ST101036, ST029248, and ST026567 exhibited higher degranulation potency than other hit compounds in both human and mouse MCs. In addition, the 15 compounds identified promote de novo synthesis of cytokines and induce the release of eicosanoids from human and mouse MCs. HTS enabled us to identify small-molecule MC activators with unique properties that may be useful as vaccine adjuvants.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

SLAS Discov

DOI

EISSN

2472-5560

Publication Date

July 2019

Volume

24

Issue

6

Start / End Page

628 / 640

Location

United States

Related Subject Headings

  • Small Molecule Libraries
  • Quality Control
  • Mice
  • Mast Cells
  • Humans
  • High-Throughput Screening Assays
  • Drug Discovery
  • Dose-Response Relationship, Drug
  • Cytokines
  • Cell Survival
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Choi, H. W., Chan, C., Shterev, I. D., Lynch, H. E., Robinette, T. J., Johnson-Weaver, B. T., … Staats, H. F. (2019). Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening. SLAS Discov, 24(6), 628–640. https://doi.org/10.1177/2472555219834699
Choi, Hae Woong, Cliburn Chan, Ivo D. Shterev, Heather E. Lynch, Taylor J. Robinette, Brandi T. Johnson-Weaver, Jianling Shi, et al. “Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening.SLAS Discov 24, no. 6 (July 2019): 628–40. https://doi.org/10.1177/2472555219834699.
Choi HW, Chan C, Shterev ID, Lynch HE, Robinette TJ, Johnson-Weaver BT, et al. Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening. SLAS Discov. 2019 Jul;24(6):628–40.
Choi, Hae Woong, et al. “Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening.SLAS Discov, vol. 24, no. 6, July 2019, pp. 628–40. Pubmed, doi:10.1177/2472555219834699.
Choi HW, Chan C, Shterev ID, Lynch HE, Robinette TJ, Johnson-Weaver BT, Shi J, Sempowski GD, Kim SY, Dickson JK, Gooden DM, Abraham SN, Staats HF. Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening. SLAS Discov. 2019 Jul;24(6):628–640.

Published In

SLAS Discov

DOI

EISSN

2472-5560

Publication Date

July 2019

Volume

24

Issue

6

Start / End Page

628 / 640

Location

United States

Related Subject Headings

  • Small Molecule Libraries
  • Quality Control
  • Mice
  • Mast Cells
  • Humans
  • High-Throughput Screening Assays
  • Drug Discovery
  • Dose-Response Relationship, Drug
  • Cytokines
  • Cell Survival