Table 1.
Validated Top Hits from Phenotypic Screen for YAP Inhibitors in Human Lung Fibroblasts
| Compound | Maximum Reduction
(%) |
First Effective Concentration
(μM) |
IC50
(μM) |
Compound Targets | |||
|---|---|---|---|---|---|---|---|
| 25 kPa | Plastic | 25 kPa | Plastic | 25 kPa | Plastic | ||
| Danusertib | 78 | 81 | 1.20 | 1.20 | 6.42 | 6.04 | Aurora A/B/C |
| PHA-680632 | 68 | 76 | 3.67 | 1.20 | ∼3.13 | 4.29 | Aurora A/B/C |
| GSK2126458 | 64 | 70 | 1.20 | 0.40 | 1.49 | 0.78 | PI3K (α/β/δ/γ) and mTORC1/2 |
| Vandetanib | 63 | 60 | 1.20 | 1.20 | N/A | 1.14 | VEGFR2, VEGFR3, and EGFR |
| Dasatinib | 61 | 59 | 0.016 | 0.016 | 1.73 | 0.28 | Abl, Src, and c-Kit |
| NVP-TAE684 | 58 | 63 | 0.14 | 0.14 | 0.10 | 0.21 | ALK |
| ALW-II-49-7 | 56 | 43 | 3.67 | 1.20 | ∼3.36 | 1.41 | EPHB2, DDR1, EPHA2, PDGFRA, EPHA5, EPHA4, EPHA3, EPHA8, KIT, PDGFRB, EPHB4, EPHB3, DDR2 |
| TWS119 | 52 | 51 | 0.40 | 0.40 | 0.41 | 0.74 | GSK-3β |
| MK-5108 | 49 | 59 | 3.67 | 3.67 | 3.08 | 4.23 | Aurora A |
| Saracatinib | 47 | 43 | 0.14 | 0.14 | 0.15 | 0.17 | Src, c-Yes, Fyn, Lyn, Blk, Fgr, and Lck |
| PF-477736 | 46 | 69 | 3.67 | 3.67 | 4.67 | ∼3.24 | Chk1, VEGFR2, Aurora A, FGFR3, Flt3, Fms (CSF1R), Ret, and Yes |
| SB 216763 | 43 | 52 | 0.14 | 0.14 | 1.73 | 0.28 | GSK-3 inhibitor |
| XL019 | 32 | 50 | 3.67 | 1.20 | 5.23 | 3.16 | JAK2 |
| PF-04691502 | 31 | 59 | 3.67 | 3.67 | ∼3.26 | ∼3.60 | PI3K (α/β/δ/γ) and mTOR |
Definition of abbreviations: IC50 = Half Maximal Inhibition Concentration; N/A = Not Available; YAP = Yes-associated protein.