Vistusertib (AZ-2014) is a dual inhibitor of mTORC1/mTORC2 which was developed by AstraZeneca for the treatment of cancer. The drug is under clinical development (phase II) in patients with Renal Carcinoma, Squamous Non Small Cell Lung Cancer, Diffuse Large B-Cell Lymphoma, Meningioma, Breast cancer and Gastric cancer, either alone or in combination therapy. Vistusertib penetrates blood-brain barrier.

AZD4017, a 11β-hydroxysteroid dehydrogenase type 1 inhibitor, has been developed by AstraZeneca for the treatment of obesity, raised intraocular pressure (IOP) and type 2 diabetes. Inhibition of 11β-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. However, studies were discontinued due to safety and efficacy reasons. Besides, specific inhibition of 11β-HSD1 can decrease intracranial pressure and consequently treat patients with Idiopathic Intracranial Hypertension (IIH), thus AZD4017 participated in phase II clinical trials to treat this disease. IIH, also known as benign intracranial hypertension or pseudotumor cerebri, is a condition of unknown etiology characterized by elevated intracranial pressure (ICP) and papilledema. In addition, AZD4017 in combination with prednisolone participated in phase II clinical trials for patients with Iatrogenic Cushing's Disease. It was postulated that the adverse metabolic effects of prednisolone could be reduced by co-administration of AZD4017.

AZD3839 is a potent and selective BACE1 inhibitor with about 14-fold selectivity over BACE2. In SH-SY5Y cells, AZD3839 efficiently decreases the Aβ40 levels and decreases the formation of sAPPβ. AZD3839 also decreases the Aβ40 levels secreted from C57BL/6 mouse primary cortical neurons, N2A cells, and Dunkin-Hartley guinea pig primary cortical neurons. AZD3839 causes in vitro BACE1 inhibition in the cell assay with the IC50 value of 16.7 nM. In C57BL/6 mice, AZD3839 (69 mg/kg, p.o.) causes a dose- and time-dependent reduction of plasma and brain Aβ. In guinea pig and non-human primates, AZD3839 also inhibits Aβ generation. AZD3839 has been used in phase I clinical trials studying the basic science of Safety and Tolerability. However future development has been discontinued.

AZD 9496 was discovered by AstraZeneca as a potent and selective estrogen receptor downregulator (SERD). This drug participated in phase I clinical trials to evaluate the pharmacokinetic profiles and the safety and tolerability of the different forms, formulations, and doses for the treatment of patients with breast cancer.

AZD-8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. AZD-8186 is currently in phase 1 clinical trials. Combination therapy using AZD-8186 with androgen deprivation results in long-lasting tumor regression, which persisted after treatment cessation.

AZD-7687 is a potent inhibitor of Diacylglycerol O-acyltransferase 1 (DGAT1) which was developed by AstraZeneca for the treatment obesity and type 2 diabetes mellitus. AZD-7687 reached phase I of clinical trials, but was discontinued by unknown reasons.

AZD5423, a non-steroidal glucocorticoid receptor agonist, was participated in clinical trials phase II for treatment of Asthma, and Chronic Obstructive Pulmonary Disease. However, the development of the product was discontinued.

AZD-8835 is a potent inhibitor of PI3Kα and PI3Kδ with selectivity versus PI3Kβ, PI3Kγ, and other kinases that preferentially inhibited growth in cells with mutant PIK3CA status, such as in estrogen receptor-positive (ER(+)) breast cancer cell lines BT474, MCF7, and T47D (sub-umol/L GI50s). Consistent with this, AZD-8835 demonstrated antitumor efficacy in corresponding breast cancer xenograft models when dosed continuously. AZD-8835 is a selective, oral inhibitor of PI3K isoforms α and δ with the following activity in enzymatic assays: PI3K α – IC50 = 6nM (equipotent vs wt and E545K / H1047R mutants); PI3K δ – IC50 = 6nM; PI3K γ – IC50 = 90nM; PI3K β – IC50 = 431nM. Inhibition of signalling in cells (pAKT endpoint): PI3K α – IC50 = 57nM; PI3K δ – IC50 = 49nM; PI3K β – IC50 = 3.6uM; PI3K γ - IC50 = 532nM. AZD-8835 is in phase I clinical studies by AstraZeneca for the treatment of advanced solid tumors and ER+ and HER-2 negative breast cancer.

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.