Table 1.
Characteristics of novel PI3K inhibitors
| Classification | Drug name | IC50 (nM) | IC50 to GBM cells (μM) | References | ||||
|---|---|---|---|---|---|---|---|---|
| p110α | p110β | p110δ | p110γ | mTORC1/2 | ||||
| Pan-PI3K inhibitors | Pictilisib (GDC-0941) | 3 | 33 | 3 | 75 | 580 | 0.95 (U-87 MG) | [63, 130] |
| Taselisib (GDC-0032) | 0.29 | 9.1 | 0.12 | 0.97 | 1200 | N/A | [131] | |
| Buparlisib (BKM120) | 52 | 166 | 116 | 262 | 4600 | 1.28 ± 0.33 (p53 wt cells) 2.08 ± 0.69 (p53 mutant/deleted cells) |
[35, 36] | |
| Pilaralisib (XL147, SAR245408) | 39 | 383 | 36 | 23 | >15,000 | 24.0 (U-87 MG) >30.0 (U-251 and U-373 MG) |
[43] | |
| Copanlisib (BAY 80–6946) | 0.5 | 3.7 | 0.7 | 6.4 | 45 | ~0.1 (U-87 MG) | [73, 132] | |
| Sonolisib (PX-866) | 0.1 | >300 | 2.9 | N/A | N/A | N/A | [52] | |
| ZSTK474 | 16 | 44 | 4.6 | 49 | >10,000 | 7.0 (U-87 MG) 1.1 (U-251 MG) |
[68, 133] | |
| AMG 511 | 4 | 6 | 2 | 1 | N/A | N/A | [70] | |
| Isoform-selective inhibitors | Alpelisib (BYL719) | 5 | 1200 | 290 | 250 | >9100 | N/A | [75] |
| Idelalisib (CAL-101, GS-1101) | 820 | 565 | 2.5 | 89 | >1000 | 39.11 (U-87 MG) | [19, 134] | |
| AMG319 | 3300 | 2700 | 18 | 850 | N/A | N/A | [135] | |
| AZD6482 | 870 | 10 | 80 | 1090 | N/A | N/A | [136] | |
| CH5132799 | 14 | 120 | 500 | 36 | 1600 | N/A | [137] | |
| AS-605240 | 60 | 270 | 300 | 8 | N/A | N/A | [138] | |
| MLN1117 (INK1117) | 15 | 4500 | 1900 | 13,390 | 1670 | N/A | [139] | |
| Dual PI3K/mTOR inhibitors | Dactolisib (NVP-BEZ235) | 4 | 75 | 7 | 5 | 6 | 0.04–0.1 | [89, 140] |
| NVP-BGT226 | 4 | 63 | N/A | 38 | N/A | N/A | [141] | |
| Omipalisib (GSK2126458, GSK458) | 0.019 | 0.13 | 0.024 | 0.06 | 0.18/0.3 | N/A | [142] | |
| GSK1059615 | 0.4 | 0.6 | 2 | 5 | 12 | N/A | [143] | |
| Voxtalisib (XL765, SAR245409) | 39 | 113 | 41 | 9 | 160/910 | 2.6 (U-87 MG) 19.6 (U-251 MG) >30 (U-373 MG) |
[100] | |
| Apitolisib (GDC-0980) | 5 | 27 | 7 | 14 | 17 | N/A | [144] | |
| GDC-0084 (RG7666) | 2 | 46 | 3 | 10 | 70 | 0.74 (U-87 MG) | [104] | |
| VS-5584 (SB2343) | 16 | 68 | 42 | 25 | 37 | 0.18 (U-87 MG) | [145] | |
| PF-04691502 | 1.8 | 2.1 | 1.6 | 1.9 | 16 | N/A | [146] | |
| Gedatolisib (PF-05212384, PKI-587) | 0.4 | N/A | N/A | 5.4 | 1.6 | N/A | [147] | |
| PKI-402 | 2 | 7 | 14 | 16 | 3 | 0.077 (U-87 MG) | [148] | |
N/A, not available