Table 1.
Synergy analysis of TPI 287 and AURKA inhibitors alisertib and TC-A2317.
| alisertib + TPI 287 | ||||||
|---|---|---|---|---|---|---|
|
| ||||||
| IC50x | alisertib (nM) | TPI 287 (nM) | Bliss | Chou-Ta | Lower CI | Upper CI |
| GB30 Colony Formation Assay (1) | ||||||
|
| ||||||
| 0.2 | 6.4 | 0.14 | NA | NA | NA | NA |
| 0.3 | 9.6 | 0.21 | NA | NA | NA | NA |
| 0.5 | 16 | 0.35 | 2.74 | 3.42 | 1.99 | 5.87 |
| 0.75 | 24 | 0.53 | 1.19 | 1.67 | 0.98 | 2.84 |
| 1 | 32 | 0.70 | 0.94 | 0.97 | 0.56 | 1.70 |
| 1.25 | 40 | 0.88 | 0.97 | 0.76 | 0.43 | 1.36 |
| 1.5 | 48 | 1.05 | 1.22 | 1.55 | 0.89 | 2.70 |
| 2 | 64 | 1.40 | 1.18 | 1.76 | 1.00 | 3.08 |
|
| ||||||
| GB30 Colony Formation Assay (2) | ||||||
|
| ||||||
| 0.2 | 6.4 | 0.14 | 3.85 | 4.05 | 1.98 | 8.30 |
| 0.3 | 9.6 | 0.21 | 3.00 | 2.86 | 1.52 | 5.39 |
| 0.5 | 16 | 0.35 | 1.63 | 2.71 | 1.50 | 4.91 |
| 0.75 | 24 | 0.53 | 0.65 | 0.48 | 0.26 | 0.89 |
| 1 | 32 | 0.70 | 0.79 | 0.62 | 0.34 | 1.15 |
| 1.25 | 40 | 0.88 | 0.94 | 0.53 | 0.28 | 0.99 |
| 1.5 | 48 | 1.05 | 0.97 | 0.50 | 0.26 | 0.96 |
| 2 | 64 | 1.40 | 1.04 | 0.63 | 0.33 | 1.21 |
|
| ||||||
| U87 Colony Formation Assay (1) | ||||||
|
| ||||||
| 0.2 | 20 | 0.15 | 1.97 | 2.63 | 1.38 | 5.04 |
| 0.3 | 30 | 0.23 | 2.53 | 3.74 | 1.96 | 7.15 |
| 0.5 | 50 | 0.38 | 2.78 | 4.55 | 2.43 | 8.53 |
| 0.75 | 75 | 0.56 | 1.83 | 3.13 | 1.74 | 5.64 |
| 1 | 100 | 0.75 | 1.21 | 1.50 | 0.86 | 2.62 |
| 1.25 | 125 | 0.94 | 0.94 | 0.44 | 0.24 | 0.80 |
| 1.5 | 150 | 1.13 | 0.96 | 0.25 | 0.13 | 0.50 |
| 2 | 200 | 1.50 | 0.97 | 0.08 | 0.03 | 0.21 |
|
| ||||||
| U87 Colony Formation Assay (2) | ||||||
|
| ||||||
| 0.2 | 20 | 0.15 | 1.49 | 1.30 | 0.32 | 5.24 |
| 0.3 | 30 | 0.23 | 0.86 | 0.99 | 0.31 | 3.17 |
| 0.5 | 50 | 0.38 | 0.78 | 1.34 | 0.44 | 4.06 |
| 0.75 | 75 | 0.56 | 1.10 | 1.34 | 0.50 | 3.60 |
| 1 | 100 | 0.75 | 0.67 | 0.51 | 0.22 | 1.15 |
| 1.25 | 125 | 0.94 | 0.88 | 0.31 | 0.12 | 0.79 |
| 1.5 | 150 | 1.13 | 0.95 | 0.24 | 0.08 | 0.68 |
| 2 | 200 | 1.50 | 0.97 | 0.00 | NA | NA |
|
| ||||||
| U1242 Colony Formation Assay (1) | ||||||
|
| ||||||
| 0.2 | 20 | 0.16 | 2.95 | 2.44 | 0.98 | 6.06 |
| 0.3 | 30 | 0.24 | 1.55 | 2.37 | 0.98 | 5.73 |
| 0.5 | 50 | 0.40 | 0.81 | 1.10 | 0.46 | 2.59 |
| 0.75 | 75 | 0.60 | 0.79 | 0.48 | 0.19 | 1.23 |
| 1 | 100 | 0.80 | 0.89 | 0.27 | 0.09 | 0.76 |
| 1.25 | 125 | 1.00 | 0.98 | 0.29 | 0.10 | 0.85 |
| 1.5 | 150 | 1.20 | 0.99 | 0.29 | 0.09 | 0.87 |
| 2 | 200 | 1.60 | 1.00 | 0.00 | NA | NA |
|
| ||||||
| U1242 Colony Formation Assay (2) | ||||||
|
| ||||||
| 0.2 | 20 | 0.16 | 0.77 | 1.43 | 0.59 | 3.45 |
| 0.3 | 30 | 0.24 | 1.26 | 1.98 | 0.83 | 4.74 |
| 0.5 | 50 | 0.40 | 1.74 | 2.55 | 1.08 | 6.02 |
| 0.75 | 75 | 0.60 | 0.95 | 1.05 | 0.45 | 2.44 |
| 1 | 100 | 0.80 | 0.96 | 0.55 | 0.23 | 1.33 |
| 1.25 | 125 | 1.00 | 0.99 | 0.69 | 0.29 | 1.66 |
| 1.5 | 150 | 1.20 | 1.01 | 0.64 | 0.26 | 1.57 |
| 2 | 200 | 1.60 | 1.00 | 0.51 | 0.20 | 1.29 |
| TC-A2317 + TPI 287 | ||||||
|---|---|---|---|---|---|---|
|
| ||||||
| IC50x | TC-A2317 (nM) | TPI 287 (nM) | Bliss | Chou-T | Lower CI | Upper CI |
| GB30 Colony Formation Assay (1) | ||||||
|
| ||||||
| 0.2 | 26.0 | 0.14 | 1.41 | 1.32 | 0.36 | 4.87 |
| 0.3 | 39.0 | 0.21 | 1.14 | 1.31 | 0.37 | 4.66 |
| 0.5 | 65.0 | 0.35 | 0.77 | 1.63 | 0.47 | 5.69 |
| 0.75 | 97.5 | 0.53 | 0.54 | 0.95 | 0.28 | 3.30 |
| 1 | 130 | 0.70 | 0.78 | 1.07 | 0.31 | 3.71 |
| 1.25 | 163 | 0.88 | 1.01 | 1.00 | 0.28 | 3.51 |
| 1.5 | 195 | 1.05 | 1.44 | 1.27 | 0.36 | 4.47 |
| 2 | 260 | 1.40 | 1.38 | 1.31 | 0.37 | 4.71 |
|
| ||||||
| GB30 Colony Formation Assay (2) | ||||||
|
| ||||||
| 0.2 | 26.0 | 0.14 | 1.53 | 1.49 | 0.55 | 4.05 |
| 0.3 | 39.0 | 0.21 | 1.07 | 1.40 | 0.54 | 3.64 |
| 0.5 | 65.0 | 0.35 | 1.17 | 2.00 | 0.78 | 5.16 |
| 0.75 | 97.5 | 0.53 | 0.73 | 1.39 | 0.56 | 3.43 |
| 1 | 130 | 0.70 | 0.72 | 0.88 | 0.36 | 2.18 |
| 1.25 | 163 | 0.88 | 0.89 | 1.06 | 0.43 | 2.62 |
| 1.5 | 195 | 1.05 | 1.04 | 0.85 | 0.33 | 2.14 |
| 2 | 260 | 1.40 | 1.06 | 0.92 | 0.36 | 2.38 |
|
| ||||||
| U87 Colony Formation Assay (1) | ||||||
|
| ||||||
| 0.2 | 25.0 | 0.15 | 10.23 | 7.27 | 2.83 | 18.65 |
| 0.3 | 37.5 | 0.23 | NA | NA | NA | NA |
| 0.5 | 62.5 | 0.38 | 1.62 | 2.27 | 1.08 | 4.77 |
| 0.75 | 93.8 | 0.56 | 1.90 | 2.42 | 1.15 | 5.06 |
| 1 | 125 | 0.75 | 1.99 | 2.67 | 1.28 | 5.59 |
| 1.25 | 156 | 0.94 | 1.05 | 1.29 | 0.60 | 2.78 |
| 1.5 | 188 | 1.13 | 0.90 | 0.30 | 0.13 | 0.71 |
| 2 | 250 | 1.50 | 0.97 | 0.12 | 0.04 | 0.31 |
|
| ||||||
| U87 Colony Formation Assay (2) | ||||||
|
| ||||||
| 0.2 | 25.0 | 0.15 | 1.05 | 1.37 | 0.29 | 6.40 |
| 0.3 | 37.5 | 0.23 | 1.89 | 2.32 | 0.48 | 11.29 |
| 0.5 | 62.5 | 0.38 | 1.50 | 2.07 | 0.50 | 8.48 |
| 0.75 | 93.8 | 0.56 | 1.83 | 2.80 | 0.69 | 11.26 |
| 1 | 125 | 0.75 | 1.19 | 2.45 | 0.64 | 9.40 |
| 1.25 | 156 | 0.94 | 0.90 | 1.39 | 0.37 | 5.25 |
| 1.5 | 188 | 1.13 | 1.14 | 1.41 | 0.37 | 5.36 |
| 2 | 250 | 1.50 | 1.01 | 0.23 | 0.06 | 0.90 |
|
| ||||||
| U1242 Colony Formation Assay (1) | ||||||
|
| ||||||
| 0.2 | 35.0 | 0.16 | 0.81 | 1.77 | 0.72 | 4.38 |
| 0.3 | 52.5 | 0.24 | 1.10 | 2.26 | 0.92 | 5.53 |
| 0.5 | 87.5 | 0.40 | 0.92 | 1.75 | 0.73 | 4.17 |
| 0.75 | 131 | 0.60 | 0.71 | 0.95 | 0.39 | 2.33 |
| 1 | 175 | 0.80 | 0.84 | 0.49 | 0.18 | 1.30 |
| 1.25 | 219 | 1.00 | 0.97 | 0.33 | 0.12 | 0.94 |
| 1.5 | 263 | 1.20 | 0.99 | 0.00 | NA | NA |
| 2 | 350 | 1.60 | 1.00 | 0.39 | 0.13 | 1.17 |
|
| ||||||
| U1242 Colony Formation Assay (2) | ||||||
|
| ||||||
| 0.2 | 35.0 | 0.16 | 1.47 | 2.01 | 0.72 | 5.60 |
| 0.3 | 52.5 | 0.24 | 1.75 | 2.80 | 1.01 | 7.73 |
| 0.5 | 87.5 | 0.40 | 0.90 | 1.51 | 0.56 | 4.05 |
| 0.75 | 131 | 0.60 | 0.96 | 0.65 | 0.22 | 1.95 |
| 1 | 175 | 0.80 | 0.98 | 0.77 | 0.25 | 2.34 |
| 1.25 | 219 | 1.00 | 1.01 | 0.87 | 0.28 | 2.68 |
| 1.5 | 263 | 1.20 | NA | NA | NA | NA |
| 2 | 350 | 1.60 | NA | NA | NA | NA |
Bliss and aChou-Talalay values < 1.0 in bold indicate synergy. 95% confidence intervals (CI) are indicated for Chou-Talalay analyses. CI < but not containing 1.0 are of higher statistical significance. When observed percent inhibition was negative or when both obs erved and expected percent inhibition were 1.0, Bliss and Chou-Talalay indices were not valid and are indicated as “NA”.