Balamapimod, also known as MKI 833, a mitogen-activated protein kinase (Ras/Raf/MEK) inhibitor with potential anti-tumor activity. This compound can be used for the treatment of diseases that are results of deregulation of Ras/Raf/MEK kinases.

Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. It also inhibits several cancer related tyrosine kinases as well as Abl, Trk-a, fibroblast growth receptor-1 and Ret. Danusertib is in phase II trials for the treatment of solid tumours, prostate cancer and chronic myeloid leukemia (CML). The most frequently reported side effects were neutropenia, nausea, anorexia, fatigue, and diarrhea.

Refametinib (RDEA-119, BAY- 869766) is a highly potent and selective inhibitor of mitogen-activated ERK kinase (MEK1/2) activity, Refametinib binds to an allosteric pocket adjacent to the ATP binding site, locking the enzyme in a catalytically inactive conformation. This compound is highly efficacious at inhibiting cell proliferation in several tumor cell lines in vitro. In vivo, Refametinib exhibits potent activity in xenograft models of cancers. Ardea Biosciences (a subsidiary of AstraZeneca) and Bayer HealthCare are developing refametinib for the treatment of cancer. The sulfonamide agent was originally developed by Valeant Pharmaceuticals International. Refametinib is in phase II development for hepatocellular carcinoma, and phase I/II development for pancreatic cancer and other solid tumours.

Ralimetinib (LY2228820), a trisubstituted imidazole derivative, is a potent and selective, ATP-competitive inhibitor of the α- and β-isoforms of p38 mitogen-activated protein kinase. LY2228820 produced significant tumor growth delay in multiple in vivo cancer models (melanoma, non-small cell lung cancer, ovarian, glioma, myeloma, breast). Eli Lilly is developing ralimetinib for the treatment of cancer.

Evobrutinib is a highly selective, irreversible inhibitor of Bruton's tyrosine kinase (BTK). It potently inhibits BCR- and Fc receptor-mediated signaling and, thus, subsequent activation and function of B cells and innate immune cells such as monocytes and basophils. Evobrutinib demonstrated effectivity in autoimmune disease preclinical models. Evobrutinib is being developed by Merck Serono for the treatment of various autoimmune disorders.

Tozasertib, originally developed as VX-680 by Vertex (Cambridge, MA) and later renamed MK-0457 by Merck (Whitehouse Station, NY), was the first aurora kinase inhibitor to be tested in clinical trials. The drug, a pyrimidine derivative, has affinity for all aurora family members at nanomolar concentrations with inhibitory constant values (Ki(app)) of 0.6, 18, and 4.6 nM for aurora A, aurora B, and aurora C, respectively. Preclinical studies confirmed that tozasertib inhibited both aurora A and aurora B kinase activity, and activity has been reported against prostate, thyroid, ovarian, and oral squamous cancer cell lines. Upon treatment with tozasertib, cells accumulate with a 4N DNA content due to a failure of cytokinesis. This ultimately leads to apoptosis, preferentially in cells with a compromised p53 function. Tozasertib is an anticancer chemotherapeutic pan-aurora kinase (AurK) inhibitor that also inhibits FMS-like tyrosine kinase 3 (FLT3) and Abl. Tozasertib is currently in clinical trials as a potential treatment for acute lymphoblastic leukemia (ALL). In cellular models of cancer, tozasertib activates caspase-3 and PARP and decreases expression of HDAC, increasing apoptosis and inhibiting cell growth. In other cellular models, tozasertib inhibits cell proliferation and metastasis by blocking downstream ERK signaling and downregulating cdc25c and cyclin B. This compound also decreases tumor growth in an in vivo model of prostate cancer.

Seliciclib (CYC202, R-roscovitine) is a second-generation orally available cyclin-dependent kinases (CDKs) inhibitor that competes for ATP binding sites on these kinases. It is a direct inhibitor of cyclin CDK2/E, CDK2/A and it has inhibitory effects on cyclin H/CDK7, CDK5, and CDK9. CDKs are enzymes that are central to the process of cell division and cell cycle control and play pivotal roles in cancer cell growth and DNA damage repair. Seliciclib exerts an anti-proliferative effect via several key mechanisms: selective downregulation of proliferative and survival proteins and upregulation of p53, leading to growth arrest or apoptosis. The second one is decreasing phosphorylation of Rb and modulating E2F transcriptional activity leading to growth arrest or apoptosis. Seliciclib is currently in phase II clinical trial as a drug candidate for the treatment of Cushing's disease and as a potential therapeutic agent for the treatment of cystic fibrosis (CF). In addition, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.

Canertinib or CI-1033 (N-[4-[N-(3-Chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazolin-6-yl]acrylamide) is a pan-erbB tyrosine kinase inhibitor. It selectively inhibits erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without inhibiting tyrosine kinase activity of receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor, even at high concentrations. Canertinib was under development by Pfizer Inc as a potential treatment for cancer.

Linsitinib is an inhibitor of the insulin receptor and the insulin-like growth factor 1 receptor, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Linsitinib is in phase II clinical trials for the treatment of metastatic prostate carcinoma, gastrointestinal stromal tumors and other cancers. Common adverse events included fatigue, nausea hyperglycaemia and anorexia.

Foretinib is an orally available multikinase inhibitor that targets c-MET and VEGFR2 with high affinity, which may result in the inhibition of tumor angiogenesis, tumor cell proliferation and metastasis. Foretinib is an experimental drug candidate for the treatment of cancer. It was in Phase II trials for the treatment breast cancer, non-small cell lung cancer, gastric cancer, head and neck cancer and papillary renal-cell carcinoma. The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli.