Daidzein, an isoflavonoid phytoestrogenic compound found in soybeans, possesses various biological properties. It may induce apoptosis of choriocarcinoma cells in a dose-dependent manner via the mitochondrial apoptotic pathway, in addition, it promotes proliferation and differentiation in osteoblastic OCT1 cells via activation of the BMP-2/Smads pathway. Daidzein exerts neuroprotective effects through the novel extranuclear GPR30 and the classical transcriptionally acting ERβ.

Cenisertib (also known as R763) is water-soluble, synthetic small molecule aurora kinase inhibitor with potential antineoplastic activity. Cenisertib is a potent adenine triphosphate-competitive inhibitor of Aurora kinase isoforms A–C, disrupting mitotic spindle activity, blocking cell separation, and leading to polyploidy and cell death. At low nanomolar concentrations, Cenisertib also inhibits other kinases involved in cell survival and proliferation including FLT3, BCR-ABL1, and BCR-ABL1 with T315I mutation. It also inhibits JAK2 kinase, but at higher concentrations. Preclinically, Cenisertib has demonstrated potent antitumor activity as a single agent and in combination treatment in leukemia cell lines, freshly isolated leukemia cells, and leukemia xenograft models. Toxicities appear to be related mainly to the gastrointestinal and hematopoietic systems. In animal models, activity and toxicity depend not only on dose but also on the schedule of administration.

Semapimod (CNI-1493) is a cytokine inhibitor and synthetic guanylhydrazone mitogen-activated protein kinase blocker, is being developed by Cytokine PharmaSciences as a potential treatment for Crohn's disease and other inflammatory conditions. As of December 2001, a phase I study demonstrating the safety of the compound had been completed and phase II trials for psoriasis and Crohn's disease were ongoing. In April 2003, preclinical and early clinical studies were underway for a variety of indications, including congestive heart failure and pancreatitis. Semapimod inhibits activation of p38 MAPK and NF-κB and induction of cyclooxygenase-2 by TLR ligands, but not by IL-1β or stresses. Semapimod inhibits TLR4 signaling (IC50 ≈0.3 umol) and acts by desensitizing cells to LPS; it fails to block responses to LPS concentrations of ≥5 ug/ml. Semapimod had been in phase II clinical trials by Ferring Pharmaceuticals for the treatment of Crohn's disease. However, this research has been discontinued. Semapimod is in phase I clinical trials for the treatment of autoimmune disorders and inflammation.

Spebrutinib (CC-292, AVL-292) is a selective inhibitor of BTK that was under clinical development for the treatment of rheumatoid arthritis (phase II) and B-cell Lymphoma (phase I). The drug was discovered by Avila Therapeutics, but then acquired by Celgene. Spebrutinib covalently binds to Cys 481 in BTK, blocking the ATP-binding pocket of the enzyme. The drug is no longer in Celgene's pipeline and its development is supposed to be terminated.

Alisertib (MLN8237) is an orally available selective aurora A kinase inhibitor developed by Takeda. Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells and produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model, a phenotype consistent with AAK inhibition. Alisertib inhibited proliferation of human tumor cell lines in vitro and produced tumor growth inhibition in solid tumor xenograft models and regressions in in vivo lymphoma models. It is currently in phase II clinical trials for acute myeloid leukaemia; B cell lymphoma; brain cancer; mesothelioma; prostate cancer; small cell lung cancer.

Dinaciclib (SCH 727965) is a small molecule inhibitor of cyclin-dependent kinases. Dinaciclib demostrates potent and selective inhibition of CDK2, CDK5, CDK1, and CDK9 activity. Dinaciclib inhibits cell cycle progression and proliferation in various tumor cell lines in vitro. Dinaciclib is a product of a drug discovery collaboration between Pharmacopeia (later Ligand Pharmaceuticals) and Schering-Plough (later Merck & Co.) that began in 1998. Dinaciclib showed promising effect in treating haematological malignancies and solid tumors.

Bafetinib (NS-187, INNO-406) is a second-generation tyrosine kinase inhibitor in development by CytRx under license from Nippon Shinyaku for treating Bcr-Abl+ leukemia's, including chronic myelogenous leukemia (CML) and Philadelphia+ acute lymphoblastic leukemia. It is a rationally developed tyrosine kinase inhibitor based on the chemical structure of imatinib, with modifications added to improve binding and potency against Bcr-Abl kinase. Besides Abl, bafetinib targets the Src family kinase Lyn, which has been associated with resistance to imatinib in CML. In preclinical studies, bafetinib was 25- to 55-fold more potent than imatinib in vitro and ≥ 10-fold more potent in vivo. Bafetinibinhibits 12 of the 13 most frequent imatinib-resistant Bcr-Abl point mutations, but not a Thr315Ile mutation. A small fraction of bafetinib crosses the blood-brain barrier, reaching brain concentrations adequate for suppression of Bcr-Abl+ cells. Data from a phase I clinical trial conducted in patients with imatinib-resistant or -intolerant CML have confirmed that bafetinib has clinical activity in this setting, inducing a major cytogenetic response in 19% of those patients in chronic phase. Currently, bafetinib is being developed in two phase II clinical trials for patients with B-cell chronic lymphocytic leukemia and prostate cancer, and a trial is in progress for patients with brain tumors. In 2005, the compound was licensed to Innovive Pharmaceuticals (acquired by CytRx Oncology in 2008) by Nippon Shinyaku on a worldwide basis, with the exception of Japan, for the treatment of CML. Orphan drug designation was assigned to the compound for the treatment of CML in the U.S in 2007 and in the E.U. in 2010. Bafetinib is in phase II for the treatment of hormone-refractory prostate cancer and chronic lymphocytic leukemia.

NMS-P937 is a selective PLK1 inhibitor. It was developed by Nerviano Medical Sciences and tested in phase I clinical trials.

Barasertib (AZD1152) is a dihydrogen phosphate prodrug of a pyrazoloquinazoline Aurora kinase inhibitor [AZD1152–hydroxyquinazoline pyrazol anilide (HQPA)] and is converted rapidly to the active AZD1152-HQPA in plasma. AstraZeneca was developing the aurora kinase inhibitor, barasertib (AZD 1152) as a therapeutic for cancer. AZD1152-HQPA is a highly potent and selective inhibitor of Aurora B (Ki, 0.36nmol/L) compared with Aurora A (Ki, 1,369nmol/L) and has a high specificity versus a panel of 50 other kinases. Consistent with inhibition of Aurora B kinase, addition of AZD1152-HQPA to tumour cells in vitro induces chromosome misalignment, prevents cell division, and consequently reduces cell viability and induces apoptosis. Barasertib (AZD1152) potently inhibited the growth of human colon, lung, and haematologic tumour xenografts (mean tumour growth inhibition range, 55% to ≥100%; P < 0.05) in immunodeficient mice. Detailed pharmacodynamic analysis in colorectal SW620 tumour-bearing athymic rats treated i.v. with Barasertib (AZD1152) revealed a temporal sequence of phenotypic events in tumours: transient suppression of histone H3 phosphorylation followed by accumulation of 4N DNA in cells (2.4-fold higher compared with controls) and then an increased proportion of polyploid cells (>4N DNA, 2.3-fold higher compared with controls). Histologic analysis showed aberrant cell division that was concurrent with an increase in apoptosis in AZD1152-treated tumours. Bone marrow analyses revealed transient myelosuppression with the drug that was fully reversible following cessation of Barasertib (AZD1152) treatment. Barasertib (AZD1152) was in phase III for the treatment of Acute myeloid leukaemia, but later these studies were discontinued.

Sotrastaurin, an orally-active, first-in-class immunomodulator, is under development by Novartis for the treatment of uveal melanoma and diffuse-large B-cell lymphoma. Sotrastaurin is a low molecular mass synthetic compound that potently inhibits the PKC α, β and the θ isoforms resulting in selective NF-κB inactivation. Sotrastaurin is a potent and selective pan-PKC inhibitor, mostly for PKCθ with Ki of 0.22 nM in a cell-free assay. Inhibition of PKC beta in B-cells results in prevention of NF-kB-mediated signaling and down regulation of NF-kB target genes. This may eventually lead to an induction of G1 cell cycle arrest and tumor cell apoptosis in susceptible tumor cells. This agent may act synergistically with other chemotherapeutic agents. PKC, a family of serine/threonine protein kinases overexpressed in certain types of cancer cells, is involved in cell differentiation, mitogenesis, inflammation, and the activation and survival of lymphocytes. Sotrastaurin is currently in phase II trials by Novartis for the treatment of large B-cell lymphoma and uveal melanoma. Sotrastaurin was in Phase II of clinical development for the prevention of acute rejection after solid organ transplantation and psoriasis, but this reseach had being discontinued.