Applications of Flow Cytometry in Drug Discovery and Translational Research
Abstract
1. Introduction
2. Hit Identification and Lead Optimization
3. Translational Research Informing the Path to the Clinic
4. Quantitative Pharmacokinetic/Pharmacodynamic Evaluation
5. Limitations and Opportunities for Flow Cytometric Techniques to Inform Early Clinical Decision-Making
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Therapeutic Property | Examples of Parameters Considered | Objective |
---|---|---|
Potency |
| Early screening hits typically lack sufficient potency for clinical activity at a feasible dose and require iterative optimization to improve potency. |
Safety and selectivity |
| Optimize primary target specificity while minimizing secondary interactions conferring safety risks. |
Pharmacokinetics and drug exposure |
| Optimization of properties that affect drug exposure in target tissues. These typically include characteristics related to absorption, distribution, metabolism, and excretion (ADME) of a molecule. |
Therapeutic functionality |
| Properties that affect the molecular mechanism of action. |
Lead Author | Disease Indication | Target | Modality | Use of Flow Cytometry |
---|---|---|---|---|
Tuijnenburg [7] | Auto-immunity | MTOR pathway (via phenotypic screen) | Small molecule | Phenotypic screen for regulators of auto-antibody production |
Schardt [11] | Virology | SARS-CoV-2 neutralizing antibodies | Antibody | Sorting of memory-specific B cell clones for expansion/antibody production |
Zhou [13] | Oncology | EGFR | Antibody | Characterization and rank ordering of antibodies based on binding affinity |
Revenko [17] | Oncology | FOXP3 | ASOs | Potency ranking of ASOs in primary cells |
McDermott [21] | Oncology | CLDN6 | Antibody/ADC | Characterize selectivity versus related family members |
Nilsson [25] | Oncology | JAK1 | Small molecule | Characterize selectivity (JAK1 vs. JAK2) |
Kirkland [28] | Virology | Shiga toxin | Antibody | Evaluate immune cell activation |
Mandrup [32] | Immuno-Oncology | N/A | Bi-specific antibody | Evaluate the effect of half-life modifications on efficacy |
Parameswaran [34] | Oncology | CD6 | ADC | Measure internalization efficiency |
Li [41] | Oncology | HER2 | ADC | ADC payload release versus target and bystander cells |
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Ullas, S.; Sinclair, C. Applications of Flow Cytometry in Drug Discovery and Translational Research. Int. J. Mol. Sci. 2024, 25, 3851. https://doi.org/10.3390/ijms25073851
Ullas S, Sinclair C. Applications of Flow Cytometry in Drug Discovery and Translational Research. International Journal of Molecular Sciences. 2024; 25(7):3851. https://doi.org/10.3390/ijms25073851
Chicago/Turabian StyleUllas, Sumana, and Charles Sinclair. 2024. "Applications of Flow Cytometry in Drug Discovery and Translational Research" International Journal of Molecular Sciences 25, no. 7: 3851. https://doi.org/10.3390/ijms25073851
APA StyleUllas, S., & Sinclair, C. (2024). Applications of Flow Cytometry in Drug Discovery and Translational Research. International Journal of Molecular Sciences, 25(7), 3851. https://doi.org/10.3390/ijms25073851