Examples of Phenotypic Screens

The Schultz group at Calibr screened 70 000 compounds from the Novartis compound collection initially for inhibition of biofilm formation in M. smegma-tis [58] and discovered a series of compoimds (TCAl, 12) that inhibits the same enzyme as BTZ043. This series of compoimds binds at the same site of the DprEl enzyme as does PBTZ169, although they are noncovalent inhibitors as 

Scientists at the Institut Pasteur Korea (IPK) used a high-content screening technology employing automated confocal fluorescent microscopy to study test compounds effects on Mtb inside macrophages. They screened 121 156 compounds from commercial sources to find 106 active compounds in this assay. 

5 Chatelain, E. and loset, J.-R. (2011) Drug Design, Development and Therapy, 5, 

9 Abdulla, S., Sagara, 1., Borrmann, S., lyAlessandro, U., Gonzalez, R., Hamel, M., Ogutu, B., Martensson, A., Lyimo, J., Maiga, H., Sasi, P., Nahum, A., Bassat, Q., Juma, E., Otieno, L., Bjorkman, A., Beck, 

15 Burrows, J., Leroy, D., Lotharius, J., and Waterson, D. (2011) Future Medicinal Chemistry, 3, 1401-1412. 

---

Differentiation is the developmental process by which early pluripotent cells acquire the features of late-stage, mature cells such as neurons, hepatocytes, or heart muscle cells. Currently, few examples of devised, highly selective, and efficient conditions for stem cell differentiation into specific homogeneous cell types have been reported because of a lack of understanding of stem cell signaling at the molecular level. Small-molecule phenotypic screens provide another means to generate desired cell types in a controlled manner. Several small molecules have been identified by this method that modulate specific differentiation pathways of embryonic or adult stem cells. 

If the genetic bases of phenotypes are known, disease risks may be assessed before disease onset. This is desirable only if preventive or therapeutic action can be taken. Otherwise, the psychological burden for the individual may be unwarranted. Ideally, preventive steps are undertaken in due time. Pre-symptomatic screening is applied, if disease prevails in famihes (for example, breast cancer and variation in estrogen receptor subunits or Hunting-ton s disease). The same is trae for prenatal and newborn screening, if family histories indicate the need (for example phenylketonuria, galactosemia, hypothyroidism). 

Example 2 In a phenotypic screen for inhibitors of the secretory pathway... 

---