Filgotinib (GLPG0634) is a highly selective JAK1 inhibitor. GLPG0634 is a promising drug candidate for the future treatment of autoimmune and inflammatory disorders. It is in phase III clinical trials (initiated mid-2016) for the treatment of rheumatoid arthritis, Crohn's disease and ulcerative colitis. Most common adverse events observed were infections, gastrointestinal disorders and nervous system disorders.

XL019 is a potent and selective JAK2 inhibitor. XL019 shows 50-fold or greater selectivity for JAK2, versus a panel of over 100 serine/threonine and tyrosine kinases, including other members of the JAK family. XL019 is non-selective for JAK2V617F or wild-type JAK2 and potently inhibits STAT3 and STAT5 phosphorylation in cells harboring either JAK2V617F or wild-type JAK2. Unfortunately, XL019 treatment was associated with the unexpected occurrence of neurotoxicity. Phase I clinical trials have been terminated.

OSI-930 (now SIM-930) is a potent, oral small-molecule receptor tyrosine kinase inhibitor, which acts predominantly against VEGF receptors (VEGFR), c-Kit, and platelet-derived growth factor receptors. OSI-930 has a pharmacokinetic-pharmacodynamic profile distinct from other RTK inhibitors, with potent antitumor activity in multiple xenograft models. OSI-930 passed through phase I clinical trial in the USA (in patients with advanced solid tumors) and recieved the clinical approval by China FDA after being out-licensed to Simcere Pharma in China.

Donafenib (CM-4307) is a derivative of sorafenib, where [1H] hydrogens on the terminal methyl group are substituted by deuterium. The drug was developed by the Chinese company Suzhou Zelgen Biopharmaceuticals. Upon oral administration, donafenib binds to and blocks the activity of Raf kinase, and inhibits Raf-mediated signal transduction pathways. This inhibits cell proliferation in Raf-expressing tumor cells. In addition, donafenib may inhibit unidentified RTKs, and thus may further block tumor cell proliferation in susceptible tumor cells. Donafenib is being investigated in phase 3 clinical trials for the treatment of 131I-refractory differentiated thyroid cancer, advanced hepatocellular carcinoma, and metastatic colorectal cancer.