Table 4.
Selected small molecule drugs targeting JAK or STAT proteins used in clinical setting or in different stages of clinical trials.
| Drug | Target protein | Stage | Application | Outcome | References | |
|---|---|---|---|---|---|---|
| JAKs | Ruxolitinib | JAK1/2 | Clinic | P. Vera, Myelofibrosis | Effective with mild toxicity | (242) |
| Tofacitinib | JAK3 > JAK1/2 | Clinic | RA | – | (243) | |
| Phase III | Chronic Plaque Psoriasis | Efficient and Safe | (244) | |||
| Fedratinib | JAK2 | Phase III | Myelofibrosis | Reduced splenomegaly, encephalopathy (toxicity) | (245) | |
| Decernotinib | JAK1/2/3, TYK2 | Phase II | RA | Improved symptoms | (246) | |
| Peficitinib | JAK1/2/3 | Phase III | RA | Safe and efficient | (247) | |
| WHI-P154 | JAK3 | Mice | Glioblastoma multiforme | Delayed tumor progress | (248) | |
| CEP-33779 | JAK2 | Mice | Colorectal cancer | Suppressed tumor growth | (249) | |
| AG 490 | JAK2 | Mice | RA | Improved symptoms | (250) | |
| Rats | CLI | Enhanced blood flow | (251) | |||
| WP1066 | JAK2 | Phase I | Brain tumors/melanoma | Underway (NCT01904123) | – | |
| Momelotinib | JAK1/2 | Phase I/II | Myelofibrosis | Effective and tolerable | (252) | |
| Cerdulatinib | JAK1/2/3, TYK2 | Phase I | CLL/B-cell NHL | Recruiting (NCT01994382) | – | |
| Filgotinib (GLPG0634) | JAK1 > JAK2/3, TYK2 | Phase II | RA | Effective, well-tolerated | (253) | |
| CD | Clinical remission | (254) | ||||
| Pacritinib | JAK2 | Phase III | Myelofibrosis | Terminated due to FDA concerns (NCT01773187) | – | |
| Baricitinib* | JAK1/2 > JAK3, TYK2 | Phase III | RA | Improved symptoms | (255) | |
| Gandotinib (LY2784544) | JAK2 | Phase II | Myeloproliferative Neoplasms | Ongoing (NCT01594723) | – | |
| TG101209 | JAK2 | Mice | Lung Cancer | Enhanced radiation effect | (256) | |
| XL019 | JAK2 > JAK1/3, TYK2 | Phase I | Myelofibrosis | Well-tolerated | (257) | |
| AT9283 | JAK2/3 | Phase II | Multiple Myeloma | No objective response | (258) | |
| AZ 960 | JAK2 | In vitro | Leukemia/Lymphoma | Growth arrest and apoptosis | (259) | |
| AZD1480 | JAK1/2 | Phase I | Solid Tumors | DLTs and lack of activity | (260) | |
| NVP-BSK805 | JAK2 > JAK1/3, TYK2 | Mice | P. Vera | Efficacious | (261) | |
| INCB018424 | JAK1/2 | Phase I/II | Myelofibrosis | Durable clinical benefits | (262) | |
| CEP-701 | JAK2 | Phase II | Myelofibrosis | Modest efficacy, but frequent GI toxicity | (263) | |
| STATs | Fludarabine† | STAT1 | Clinic | B-cell chronic lymphocytic leukemia | – | (264) |
| S3I-201 | STAT3 > STAT1/5 | Mice | Breast cancer | Breast tumor regression | (265) | |
| STA-21 | STAT3 | Phase I/II | Psoriasis | Improvement of lesions with topical treatment | (266) | |
| OPB-51602 | STAT3 | Phase I | Hematologic and solid malignancies | Promising antitumor activity in NSCLS | (267) | |
| OPB-31121 | STAT3 | Phase I | Advanced solid tumors | Antitumor activity | (268) | |
| HO-3867 | STAT3 | Mice | Ovarian Cancer | Inhibition of tumor growth | (269) | |
| SH-4-54 | STAT3 > STAT5 | Mice | Glioma/Breast cancer | Inhibition of tumor growth | (270) | |
| SH5-07 | STAT3 | Mice | Glioma/Breast cancer | Inhibition of tumor growth | ||
| Niclosamide‡ | STAT3 | Mice | Head and neck cancer | Inhibition of tumor growth | (271) | |
| Cryptotanshinone | STAT3 | Mice | Liver cancer | Effective STAT3 inhibition | (272) | |
| Stattic | STAT3 | Mice | ESC Carcinoma | Radio-sensitization | (273) |
CD, Crohn's disease; CLI, critical limb ischemia; CLL, chronic lymphocytic leukemia; DLT, dose-limiting toxicity; ESC, esophageal squamous cell; GI, gastrointestinal; NHL, non-Hodgkin lymphoma; NSCLS, non-small-cell lung cancer; P. Vera, Polycythemia Vera; RA, rheumatoid arthritis.
Baricitinib was approved for treatment of RA by European Commission in 2017.
Fludarabine is a chemotherapeutic agent (purine analog) that primarily targets ribonucleotide reductase and inhibits DNA synthesis. However, an inhibitory effect on STAT1 has also been reported (274).
Niclosamide is a well-known anthelmintic agent (especially against tape worms) that has shown selective inhibition of STAT3.