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.

AZD-3759 is an oral inhibitor of both wild-type and mutant EGFR with IC50 values in nanomolar range. The drug was discovered by AstraZeneca for the treatment of non-small-cell lung cancer with CNS metastases. AZD-3759 can penetrate the blood-brain barrier and was confirmed to be effective in vitro with NSCLC cell lines as well as in mouse model of brain metastases. AZD-3759 is currently in Phase 1 clinical trial.

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.

AstraZeneca was developing AZD-2066, a metabotropic glutamate receptor 5 (mGLUR5) antagonist, for the oral treatment of pain indications (e.g. chronic neuropathic pain and painful diabetic neuropathies), depressive disorders and gastro-oesophageal reflux disease. AZD-2066 had been in phase II clinical trials by AstraZeneca for the treatment of diabetic neuropathic pain and phase I for the treatment of gastrooesophageal reflux disease (GERD). However, this reasearch had being discontinued.

AZD-3514 is a down-regulator of androgen receptors. The drug was synthesized by AstraZeneca for the treatment of castrate-resistant prostate cancer and even reached phase I, however, its development was terminated.

AstraZeneca was developing AZD-2066, a metabotropic glutamate receptor 5 (mGLUR5) antagonist, for the oral treatment of pain indications (e.g. chronic neuropathic pain and painful diabetic neuropathies), depressive disorders and gastro-oesophageal reflux disease. AZD-2066 had been in phase II clinical trials by AstraZeneca for the treatment of diabetic neuropathic pain and phase I for the treatment of gastrooesophageal reflux disease (GERD). However, this reasearch had being discontinued.

AZD-1208 is an orally available, potent and highly selective Pim inhibitor that effectively inhibits all three isoforms. AZD-1208 inhibits the growth of several AML cell lines and sensitivity correlates with the level of Pim-1 expression, STAT5 activation and presence of protein tyrosine kinase mutation. AZD-1208 causes cell cycle arrest and apoptosis in MOLM-16 cells in culture. This is accompanied by a dose-dependent reduction in phosphorylation of BAD, 4EBP1 and p70S6K. In addition, AZD-1208 leads to potent inhibition of colony growth of primary AML cells from bone marrow aspirates and downregulates phosphorylation of Pim targets. AZD-1208 was in Phase 1 trials to evaluate the safety and tolerability profile and to determine the maximum tolerated dose (MTD). There were two trials where AZD-1208 had been administered orally in AML and solid tumour (of all types) patients. The studies had being discontinued due to safety reasons.

Atecegetran metoxil (more widely known as AZD0837), an anticoagulant and a prodrug, converted to a selective and reversible direct thrombin inhibitor (AR-H067637). Atecegetran metoxil participated in phase II clinical trials to prevent the stroke and systemic embolism in patients with non-valvular atrial fibrillation. The development of atecegetran metoxil was discontinued, due to a limitation identified in the long-term stability of the extended-release drug product.

Avelestat, also known as AZD9668, is a novel, oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms, and disease progression in NE-driven respiratory diseases such as bronchiectasis, Cystic Fibrosis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. Its development was discontinued due to unknown reasons. Nevertheless, this drug in the phase II of clinical trial as adjunctive therapy in improving insulin sensitivity of insulin-resistant type 2 diabetic subjects. The drug's clinical profile suggests that it will be well tolerated with few, if any, side effects, and the existence of simple methods that can indirectly measure its activity in vivo.

FLAVODILOL is an antihypertensive agent.