At EDDC’s state-of-the-art High Throughput Screening (HTS) platform, the primary goal is to rapidly identify high-quality hit compounds, and support their optimization to patentable novel drug structures.
CAPABILITIES & RESOURCES
A team of capable and experienced scientists with a broad range of assay expertise conducts an average of 10 screening campaigns annually. Assay expertise includes:
| Target Class | Signal Transduction/Receptor |
| Bacterial Phenotypic/Whole Cell Screen | Methyltransferase |
| Bacterial Protease Activator | Kinases |
| Bacterial Protease Inhibitor | Bacterial Methyltransferase |
| Zinc Finger Protein | Ion Channel |
| Gastric Cancer Phenotypic Screen | Bacterial Energy Production Pathway |
| Bacterial Cell Division Protein | GPCR |
| Amino Acid Metabolism/Energy Production | Protein-Protein Interaction |
| Signal Transduction | Cyclin Dependent Kinase |
| Viral Target | GTPase |
| Amino Acid Metabolism | Viral Methyltransferase |
- Our fully integrated automation platform comprising of >10 instruments can provide nano- & micro-liter dispensing in 96-/384-/1536-well plates for various assay readouts in alignment with the tailored project requirements.
Our unique automation configuration can support:
- Screening of up to 16,000 compounds per day for biochemical assays
- Miniaturisation of bioassays for high throughput and cost reduction by reducing typical biochemical screen volumes down to 6-12 µL per well
| Microplate Stacker | Reagent Dispenser |
| Contactless Compound Spotter | Microplate Washer |
| Tip-based Liquid Handler | Mini Centrifuge |
| Barcode Labeller | Microplate Reader |
| Microplate Carousel | Microplate Sealer |
| Microplate Peeler | And more… |
- The HTS workflows are complemented with in-house developed HTS & compound management programme (PharmApps) integrated with FDA-compliant HTS data analysis & storage database (IDBS ActivityBase).
SUCCESS STORY
EDDC’s compound collection and HTS expertise have played a pivotal role in the identification of Singapore’s 1st publicly funded anti-cancer drug, showcasing our ability to achieve remarkable results even with a collection 10 times smaller than those of major pharmaceutical companies (see below).
Discovery of WNT secretion inhibitor, ETC-159. A 225K compounds screening campaign followed by filtering through a series of specific assays led to the identification of WNT secretion inhibitors.
PUBLICATIONS
HTS (Publications related to screening campaigns & workflow)
- Chong DN, Yap A, Goh C, Choong ML, Tan SH. PharmApps: An integrated management application for tracking compound stamping and usage in high throughput screens. Biomed J Sci & Tech Res. 2020; 25(2): 18906-18916.
- Zhong W, Koay A, Ngo A, Li Y, Nah Q, Wong YH, Chionh YH, Ng HQ, Koh-Stenta X, Poulsen A, Foo K, McBee M, Choong ML, El Sahili A, Kang C, Matter A, Lescar J, Hill J, Dedon P. Targeting the bacterial epitranscriptome: Discovery of novel tRNA-(N1G37) methyltransferase (TrmD) inhibitors with antibiotic activity. ACS Infectious Diseases. 2019; 5(3): 326-335.
- Huang C, Liew S, Lin G, Poulsen A, Ang M, Chia B, Chew S, Kwek Z, Wee J, Ong E, Retna P, Baburajendran N, Li R, Yu W, Koh-Stenta X, Ngo A, Manesh S, Fulwood F, Ke Z, Chung H, Sepramaniam S, Chew X, Dinie N, Lee MA, Chew Y, Low CB, Pendharkar V, Manoharan V, S, Sangthongpitag K, Joy J, Matter A, Hill J, Keller T, Foo K. Discovery of Irreversible Inhibitors Targeting Histone Methyltransferase, SMYD3. ACS Med Chem Lett. 2019; 10(6):978-984.
- Shetty A, Xu Z, Lakshmanan U, Hill J, Choong ML, Chng SS, Yamada Y, Poulsen A, Dick T, Gengenbacher M. Novel acetamide indirectly targets mycobacterial transporter MmpL3 by proton motive force disruption. Front. Microbiol. 2018, 9: 2960.
- Ngo A, Koay A, Pecquet C, Diaconu CC, Jenkins DA, Shiau AK, Constantinescu SN, Choong ML. Phenotypic screening for inhibitors of a mutant thrombopoietin receptor. In: Wagner B (ed.), Phenotypic Screening: Methods and Protocols. Methods in Molecular Biology. 2018; Vol 1787: 53-66. Humana Press, New York, NY.
- Ngo A, Koay A, Pecquet C, Diaconu CC, Ould-Amer Y, Huang Q, Kang C, Poulsen A, Lee MA, Jenkins D, Shiau A, Constantinescu SN, Choong ML. A Phenotypic Screen for Small-Molecule Inhibitors of Constitutively Active Mutant Thrombopoietin Receptor Implicated in Myeloproliferative Neoplasms. Comb. Chem. High T. Scr. 2016; 19: 824-833.
- Moreira W, Ngan G, Low JL, Poulsen A, Chia B, Ang M, Yap A, Fulwood J, Lakshmanan U, Lim J, Khoo A, Flotow H, Hill J, Raju R, Rubin EJ, Dick T. Target mechanism-based whole-cell screening identifies bortezomib as an inhibitor of caseinolytic protease in mycobacteria. mBio. 2015 6(3): e00253-15.
- Lakshmanan U, Yap A, Fulwood J, Li Y, Sim SH, Lim J, Ting A, Sem XH, Kreisberg JF, Tan P, Tan G, Flotow H. Establishment of a novel whole animal HTS technology platform for melioidosis drug discovery. Comb. Chem. High T. Scr. 2014; 17: 790-803.