EMT / mesenchymal druggability
What this is
Table S9 measures all 92 clinical kinase inhibitors against 47 mesenchymal-specific kinases — the druggable TGF-β/BMP receptor module (ALK5/TGFBR1, TGFBR2, BMPR2, ACVR1) plus AXL, MET, DDR2, PDGFRA/B, FGFR1, EPHA2, NUAK1, LATS2 and PEAK1. Residual activity is reported as a percentage (lower = stronger inhibition); we rank drugs by inhibition weighted by each kinase’s Table S8 mesenchymal fold-change, so coverage of the most mesenchymal-enriched kinases counts for more than the naive average.
25 inhibitors by mesenchymal-program coverage
| Drug | Weighted inhibition % | Mean inhibition % | Strong hits | Coverage |
|---|---|---|---|---|
| Gilteritinib | 48.8 | 45.4 | 16/47 | 34% |
| Pacritinib | 48.7 | 45.4 | 17/47 | 36% |
| Ponatinib | 47.0 | 46.1 | 18/47 | 38% |
| Midostaurin | 45.5 | 41.7 | 16/47 | 34% |
| Sunitinib | 45.1 | 40.0 | 14/47 | 30% |
| Bosutinib | 44.2 | 41.5 | 15/47 | 32% |
| Nintedanib | 43.4 | 36.1 | 13/47 | 28% |
| Brigatinib | 39.5 | 37.3 | 13/47 | 28% |
| Repotrectinib | 38.4 | 36.4 | 13/47 | 28% |
| Crizotinib | 35.8 | 36.7 | 15/46 | 33% |
| Fedratinib | 35.4 | 29.9 | 9/47 | 19% |
| Defactinib | 35.0 | 34.1 | 12/47 | 26% |
| Tivozanib | 34.4 | 30.1 | 12/47 | 26% |
| Dasatinib | 32.7 | 32.9 | 12/47 | 26% |
| Selpercatinib | 31.8 | 26.0 | 6/47 | 13% |
| Pralsetinib | 31.4 | 25.8 | 9/47 | 19% |
| Ripretinib | 31.3 | 30.4 | 13/47 | 28% |
| Axitinib | 30.5 | 25.0 | 7/47 | 15% |
| Fostamatinib | 30.2 | 29.3 | 8/47 | 17% |
| Cabozantinib | 27.7 | 24.0 | 8/47 | 17% |
| Vandetanib | 26.9 | 25.8 | 11/47 | 23% |
| Alectinib | 25.1 | 21.8 | 4/47 | 9% |
| Entrectinib | 25.0 | 20.2 | 7/47 | 15% |
| Erdafitinib | 25.0 | 22.4 | 9/47 | 19% |
| Abemaciclib | 24.9 | 26.1 | 7/47 | 15% |
Measured vs inferred — reversal cross-validation
A consistency gate between the S9 measured anti-mesenchymal coverage and the pathway-reversal model’s inferred effect on the EMT hallmark pathway. Both axes derive from the same inhibition data, so agreement is a self-consistency check, not independent corroboration; per-drug divergence is a flag, not a verdict.
| Drug | Measured weighted % | Inferred EMT reversal | Measured rank | Inferred rank |
|---|---|---|---|---|
| Gilteritinib | 48.8 | 3241.138 | 1 | 6 |
| Pacritinib | 48.7 | 4472.965 | 2 | 1 |
| Ponatinib | 47.0 | 2482.395 | 3 | 14 |
| Midostaurin | 45.5 | 4119.324 | 4 | 2 |
| Sunitinib | 45.1 | 2977.581 | 5 | 8 |
| Bosutinib | 44.2 | 2937.450 | 6 | 9 |
| Nintedanib | 43.4 | 2916.275 | 7 | 10 |
| Brigatinib | 39.5 | 3787.639 | 8 | 3 |
| Repotrectinib | 38.4 | 2897.395 | 9 | 11 |
| Crizotinib | 35.8 | 1822.435 | 10 | 24 |
| Fedratinib | 35.4 | 2280.210 | 11 | 15 |
| Defactinib | 35.0 | 3661.890 | 12 | 4 |
| Tivozanib | 34.4 | 1595.725 | 13 | 33 |
| Dasatinib | 32.7 | 2130.145 | 14 | 19 |
| Selpercatinib | 31.8 | 1807.265 | 15 | 25 |
| Pralsetinib | 31.4 | 2732.200 | 16 | 12 |
| Ripretinib | 31.3 | 1709.255 | 17 | 28 |
| Axitinib | 30.5 | 1616.685 | 18 | 32 |
| Fostamatinib | 30.2 | 2192.737 | 19 | 18 |
| Cabozantinib | 27.7 | 1161.510 | 20 | 45 |
| Vandetanib | 26.9 | 1696.150 | 21 | 29 |
| Alectinib | 25.1 | 2483.220 | 22 | 13 |
| Entrectinib | 25.0 | 1651.190 | 23 | 31 |
| Erdafitinib | 25.0 | 1445.045 | 24 | 40 |
| Abemaciclib | 24.9 | 3511.259 | 25 | 5 |