Sapitinib is an oral, reversible and equipotent inhibitor of EGFR, HER2 and HER3 signalling. The drug was tested in phase II of clinical trials in patients with breast cancer, colorectal cancer, gastric cancer and NSCL carcinoma, however its development for breast cancer therapy seems to be terminated. Sapitinib absorption is rapid and the drug is totally cleared by metabolism with the major routes being oxidation and amine or ether cleavage around the piperidine ring with subsequent glucuronide or sulphate conjugation.

GZD824 is a novel orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 of 0.34 nM and 0.68 nM, respectively. In vivo efficacy studies in mouse xenograft or allograft models of human leukemia demonstrated that GZD824 successfully suppressed the growth of tumors driven by native Bcr-Abl, Bcr-Abl T315I, Bcr-Abl G250E, Bcr-Abl Q252H, Bcr-Abl E255K and Bcr-Abl F317L. GZD824 also provided a significant survival benefit leukemia model mice allografted with luciferase-expressing Ba/F3 cells driven by the mutant Bcr-Abl T315I kinase. The potential for compound GZD824 to overcome all of the Bcr-Abl mutations that result in clinically acquired resistance to imatinib indicates that this novel Bcr-Abl inhibitor is a promising lead candidate for further development. GZD824 has also being shown to suppresses pre-B ALL cells through inhibition of the SRC kinase and PI3K/AKT pathways and may be a potential therapeutic agent for the management of pre-B ALL.

Delparantag is a novel, salicylamide-derived, small molecule. Delparantag is heptagonist. It acts as universal anticoagulation-reversing agent. Delparantag neutralized the antithrombotic, anticoagulant, and bleeding effects of heparins as effectively as protamine sulfate and may be slightly more efficacious against low-molecular-weight heparins (LMWHs). This agent was designed to restore coagulation by specifically binding to the pentasaccharide and disrupting unfractionated heparin and LMWH interaction with antithrombin. Delparantag has been shown to completely reverse the anticoagulant effects of heparin and normalize blood-clotting time in six human subjects in less than 10 minutes in a phase IB clinical trial. In clinical trial studies, safety was ascertained by blood pressure measurements and efficacy was determined by measuring blood clotting time (aPTT, Activated Partial Thromboplastin Time, or ACT, Activated Coagulation Time). Plasma half-life elimination of delparantag is between 3 and 5 min. Development was recently paused due to hypotension noted in the studies although this may be avoided with longer administration times and will require further investigation.

Prazarelix is gonadorelin (GnRH) antagonist. It is primarily used in assisted reproduction to control ovulation. The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

ABT-510 is an anti-angiogenesis compound that was under development by Abbott for the treatment of solid tumours, lymphoma and melanoma. It is a synthetic peptide that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). ABT-510 inhibits the actions of several pro-angiogenic growth factors important to tumor neovascularization; these pro-angiogenic growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)), hepatocyte growth factor (HGF), and interleukin 8 (IL-8).

PH-797804 is a diarylpyridinone inhibitor of p38alpha mitogen-activated protein. The drug was developed by Pfizer for the treatment of inflammatory diseases. PH-797804 is being tested in phase II of clinical trials in patients with COPD, osteoarthritis, rheumatoid arthritis and post-herpetic neuralgia.

CBP-501 is a chemically modified duodecapeptide and an analog of M-phase inducer phosphatase 3 (CDC25C) that increase cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatin cytotoxicity, and affects cell cycle progression by abrogating DNA repair at the G2 checkpoint. CBP501 selectively inhibits the kinases MAPKAP-K2, C-TAK1, and CHK1 in vitro. Cell lines exposed to CBP501 plus bleomycin show a dose-dependent reduction of phosphorylated Ser216 on CDC25C. In addition to these effects on the G2 checkpoint, CBP501 also increases platinum concentration and DNA-platinum adduct formation in tumor cells through binding with calmodulin. In an in vitro panel testing the sensitivity of several tumor-derived cell lines to CBP501 in combination with a variety of anti-cancer agents, the combination of CBP501 with cisplatin was particularly effective against all four mesothelioma cell lines tested. Unfortunately, CBP-501 does not improve the efficacy of standard chemotherapy for malignant pleural mesothelioma.

Ularitide is a recombinant form of urodilatin, a natriuretic peptide synthesized in the distal tubular cells of the kidney. It regulates renal sodium and water excretion through binding to natriuretic peptide type A receptors, increasing intracellular cyclic guanosine monophosphate (cGMP) levels. While these effects, as well as others such as vasodilation, are also exhibited by other natriuretic peptides, urodilatin has a terminal extension that brings resistance to biological inactivation by neutral endopeptidase, whose activity is increased in decompensated heart failure. Animal studies have demonstrated enhanced diuresis and natriuresis and reduced PCWP (pulmonary capillary wedge pressure) and systemic vascular resistance relative to atrial natriuretic peptide (ANP [99-126], the active circulating isoform). When injected into the blood, ularitide appears to cause diuresis (urine output) and natriuresis (sodium excretion), as well as vasodilation. Ularitide is currently in Phase 3 development as a potential treatment for patients with acute decompensated heart failure (ADHF).