Drug panel 1
Organized working page for motor neurons, sensory neurons, dopamine neurons, and iPSCs. Neuron response summaries use tubulin-based neurite readouts; iPSC summaries use CellTiter-Glo viability.
Readout note
For iPSCs, CellTiter-Glo and related viability readouts work well as standard dose-response assays. For neurons, those assays do not show a reliable CellTiter-Glo dose response, so the primary neuron summary here is the percentage or fraction of neurons with neurites based on tubulin staining.
Fraction neurons by tubulin: NUCLEI CV INT WVU > 0.11.
> when the exact fit is not useful.
Reference snapshot
| Compound | EC | 40x Imaging | New BRB Seq | ||
|---|---|---|---|---|---|
| Motor dose nM | Sensory dose nM | Motor dose nM | Sensory dose nM | ||
| Brefeldin A | EC25 | 50 | 50 | 30 | 30 |
| Brefeldin A | EC75 | 60 | 60 | 72 | 72 |
| Rotenone | EC25 | 670 | 660 | 240 | 600 |
| Rotenone | EC75 | 3,710 | 3,710 | 3,700 | 2,900 |
| Thapsigargin | EC25 | 2,190 | 2,190 | 2,200 | 2,100 |
| Thapsigargin | EC75 | 2,840 | 2,840 | 3,200 | 3,700 |
| Tunicamycin | EC25 | 550 | 550 | 850 | 1,000 |
| Tunicamycin | EC75 | 5,810 | 5,810 | 1,400 | 2,800 |
| Vps34-IN-1 | EC25 | 2,680 | 2,680 | 2,000 | 300 |
| Vps34-IN-1 | EC75 | 4,800 | 4,800 | 6,000 | 5,000 |
Motor neurons
Shared panel 2 image
Anisomycin and MG-132 values for the panel 2 motor and sensory curves.
| Compound | EC25 | EC50 | EC75 | R2 |
|---|---|---|---|---|
| Anisomycin | > ~125 | |||
| MG-132 | 42.1 | 56.9 | 76.9 | 0.83 |
| Compound | EC25 | EC50 | EC75 | R2 |
|---|---|---|---|---|
| Anisomycin | 7.3 | 29.2 | 117.0 | 0.87 |
| MG-132 | 48.6 | 74.3 | 113.8 | 0.91 |
Sensory neurons
Dopamine neurons
WT and TDP43 non-production run, so this should be treated as unofficial.
iPSC
Values are usually from WT or averaged from a few genotypes, in nM.
| Compound | EC10 | EC25 | EC50 | EC75 | EC90 |
|---|---|---|---|---|---|
| Brefeldin A | 19.6 | 28.9 | 42.6 | 62.8 | 92.5 |
| Rotenone | 89.1 | 138.0 | 216.0 | 343.0 | 552.0 |
| Thapsigargin | 4.1 | 4.7 | 5.3 | 6.1 | 7.0 |
| Tunicamycin | 77.6 | 111.0 | 158.0 | 225.0 | 321.0 |
| Vps34-IN-1 | 241.0 | 611.0 | 1,549.0 | 3,928.0 | 9,963.0 |
Source: FIW105 iPSC EC Values 01.csv.
CTG versus nuclei notes belowFor iPSCs, live-cell count is the best imaging correlate with CellTiter-Glo. Total object count is a close second. These produce excellent dose response curves.
While CellTiter-Glo and live nuclei are correlated, they both change within a condition, and are poor indicators of neuronal health.
Sources (FIVE@MGI)
R:\FIVE\EXP\FIW103\P41-46\2 MlModels\DoseResponse_MG132_Tubulin_Analysis\simple1\FIW103_simple1_motor_sensory_EC_values.xlsxR:\FIVE\EXP\FIW118\P12-13\FIW118 P12 UnOfficial Dose Response Dopa.pngR:\FIVE\EXP\FIW105\P7-8\FIW105 iPSC Dose Response Summary.pngR:\FIVE\EXP\FIW105\P7-8\2 MlModels\iPSC Dose Response Outputs\FIW105 iPSC EC Values 01.csvR:\FIVE\EXP\FIW107\z107_112\Org\PPT Master\NRP_CTG_PRLog_vs_Nuclei_Survival_candidates.pptx