Sitravatinib (MGCD516) is a receptor tyrosine kinases (RTK) inhibitor that blocks a wide array of RTKs known to be amplified/overexpressed in sarcomas, which are key regulators of signaling pathways that lead to cell growth, survival and tumor progression. It is involved in driving sarcoma cell growth with IC50 of 3980 nM and is superior to other multi-kinase inhibitors in inhibiting cell proliferation, RTK phosphorylation, and phosphorylation of downstream effectors. The efficacy of sitravatinib was tested using a wide panel of sarcoma cell lines, including malignant peripheral nerve sheath tumor (MPNST), Ewing sarcoma (A673), osteosarcoma (Saos2), and liposarcoma (DDLS, LS141). Both in vitro and in vivo efficacy sitravatinib was significantly better that the other two multi-kinase inhibitors, imatinib and crizotinib. Sitravatinib treatment not only inhibits tumor cell proliferation at low nanomolar concentrations in vitro but also results significant tumor growth suppression in vivo in mouse xenograft models. Sitravatinib is being evaluated in a Phase 1b dose expansion cohort in selected patients with specific genetic alterations that are drivers of tumor growth, with an initial focus on Non-Small-Cell Lung carcinoma (NSCLC) and in other solid tumors where sitravatinib may confer a benefit. Its efficacy and safety is also being tested in Phase II clinical trials in patients with advanced liposarcoma as a monotherapy and NSCLC in combination with nivolumab.

Tirabrutinib (also known as ONO-4059 or GS-4059), a second-generation, enhanced-selectivity Bruton's tyrosine kinase inhibitor that demonstrated antitumor activity in preclinical models. Tirabrutinib participated in phase I clinical trial in patients with relapsed or refractory B-cell malignancies, where it was well tolerated and showed promising efficacy. In addition, tirabrutinib is involved in phase II clinical trials to study safety and efficacy in adults with Active Sjogren's syndrome and in adults with chronic lymphocytic leukemia. Besides the drug was studied for the treatment of Waldenstrom's macroglobulinemia and patients with refractory pemphigus.

PF-06700841 is an inhibitor of JAK1 and TYK2 kinases. PF-06700841 tosylate salt is potentially a treatment of systemic lupus erythematosus and plaque psoriasis.

R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM. R428 was originated in Rigel Pharmaceuticals and was licensed to BerGenBio, which initiated clinical trials for the treatment of non-small cell lung cancer, metastatic melanoma and acute myeloid leukaemia.

G-0853 (also GDC-0853, or Fenebrutinib) is a potent, selective, orally administered, and noncovalent Bruton's tyrosine kinase (Btk) inhibitor currently in clinical development. Upon administration, G-0853 inhibits the activity of Btk and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and Btk-mediated activation of downstream survival pathways, which leads to the inhibition of the growth of malignant B-cells that overexpress BTK. BTK is overexpressed in B-cell malignancies, and plays an important role in B-lymphocyte development, activation, signaling, proliferation and survival. G-0853 suppresses B cell- and myeloid cell-mediated components of disease and demonstrates dose-dependent activity in an in vivo rat model of inflammatory arthritis. G-0853 demonstrates highly favorable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2 studies ongoing in patients with rheumatoid arthritis, lupus, and chronic spontaneous urticaria.

Solcitinib (also known as GSK2586184 or GLPG0778) is a selective Janus kinase 1 (JAK1) inhibitor, for the treatment of psoriasis, lupus, and ulcerative colitis. Galapagos NV's collaboration with GlaxoSmithKline has hit a roadblock. It was reported that its Big Pharma partner had hit the brakes on a Phase II study of GSK2586184 for lupus after a first look at the data failed to demonstrate a positive effect. And an exploratory Phase I/II of the same drug for ulcerative colitis was put on hold as investigators review the program.