Table 2.
Pharmacologic inhibitors of STAT3 signaling investigated in glioma.
| Agent | Mechanism | Evidence of Efficacy in Glioma | Notes | References |
|---|---|---|---|---|
| G6 | JAK2 | In vitro | In vivo studies lacking, therapeutic requirement for JAK2 overexpression | [211] |
| SAR317461 | JAK2 | In vitro | In vivo studies lacking, compensatory autophagy | [212] |
| AZD1480 | JAK1/JAK2 | In vitro In vivo |
Unacceptable dose-limiting toxicities | [150,216,217] |
| JSI-124 | JAK2 | In vitro In vivo |
Anti-proliferative, immune modulatory | [213,214,215] |
| Pacritinib | JAK2 | In vitro In vivo |
BBB penetrant, chemosensitizing | [94,218] |
| * Ruxolitinib | JAK1/JAK2 | In vitro In vivo |
BBB penetrant, anti-proliferative, radiosensitizing, immune modulatory | [219,220] |
| PY * LKTK | STAT3 | In vitro | In vivo studies lacking, low potency | [222] |
| LLL12 | STAT3 | In vitro In vivo |
Potent, low solubility/poor bioavailability, unclear BBB penetrance | [223,224] |
| STX-0119 | STAT3 | In vitro In vivo |
Minimal growth inhibition of GBM in mouse model | [225,226] |
| AG490 | STAT3, JAK2 | In vitro | Low potency, in vivo efficacy lacking | [73,236] |
| Stattic | STAT3, STAT1, STAT2 | In vitro | Susceptible to intracellular modification, in vivo efficacy lacking, low specificity | [232,233,234,235] |
| WP1193 | STAT3, JAK2 | In vitro | In vivo efficacy data lacking | [240] |
| SH-4-54 | STAT3 STAT5 |
In vitro In vivo |
BBB penetrant, potent, specific, in vivo studies in subcutaneously implanted GBMs | [237,238,239] |
| * Napabucasin (BBI608) | STAT3 | In vitro In vivo |
Bioavailable, BBB penetrant | [242,243] |
| * WP1066 | STAT3, JAK2 | In vitro In vivo |
Bioavailable, BBB penetrant, immune modulatory | [73,122,241] |
* Currently being evaluated in clinical trials.