AZD5672 was developed by AstraZeneca for the treatment of rheumatoid arthritis. It was found that the drug inhibits P-glycoprotein and is a CCR5 antagonist. Exists hypothesis that inhibition of CCR5 can bring benefits in the treatment of rheumatoid arthritis. In July 2009, Phase-II for Rheumatoid arthritis was discontinued.

AZD-1981, developed by AstraZeneca, is a potent (binding IC50 of 4nM), fully reversible, functionally non-competitive antagonist of human CRTh2. It blocks agonist-induced human eosinophil CD11b expression, shape change (including in whole blood), and chemotaxis as well as an basophil shape change and Th2-cell chemotaxis at IC50's of 8.5-50nM. Potency is similar across species as is plasma protein binding (~97%). AZD-1981 is a weak (10s of μM) inhibitor in vitro of CYP2C9, OATP1B1 and UGT1A1 as well as an inducer of CYP3A4. AZD-1981 was well tolerated and no safety concerns were identified.There was no beneficial clinical effect of AZD-1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD-1981 has being discontinued for asthma and chronic obstructive pulmonary disease. AstraZeneca is collaborating with Johns Hopkins University for the development of AZD-1981 in the treatment of chronic idiopathic urticaria. It is in phase II clinicals studies for the treatment of Urticaria.

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.

AZD8055 is a new ATP-competitive mTOR kinase inhibitor that was developed to overcome the limitations of the first generation of allosteric mTORC1 inhibitors (rapamycin and its analogs) as anticancer agents. AZD8055 potently and selectively inhibits mTOR by directly targeting its catalytic site, which results in the blockade of the activity of both mTORC1 and mTORC2 complexes. It displays antitumoral activity by inhibiting proliferation and/or inducing cell death in various cancer cell models, including ovarian clear cell carcinoma.

Ponalrestat is the inhibitor of aldehyde reductase 2 from a number of sources. Ponalrestat blunted Prostaglandin F2 alpha synthesis by preadipocytes in basal and stimulated conditions. Ponalrestat suppresses IL-1 production both in vitro and in vivo, and inhibits the cachectic symptoms induced by colon26 adenocarcinoma in mice, suggesting that ponalrestat has a therapeutic potential for the treatment of cancer cachexia. In a 4-week study of 29 neuropathic diabetics treated with ponalrestat peripheral neuropathy did not improve during treatment. In a 6-week study of 21 diabetics without neuropathy, although vagal function improved in patients with autonomic neuropathy.

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-7762 for the treatment of solid tumours. AZD-7762 is a potent inhibitor of Chk1 that binds in the ATP binding pocket (IC50 of 5nM; Ki of 3.6nM). AZD-7762 has activity on a range of other kinases {examples with a < 5 fold selectivity included Rous sarcoma oncogene cellular homolog (SRC) family members (e.g., Fgr, Fyn, lymphocyte-specific protein-tyrosine kinase [Lck], and Lyn, but not SRC), Flt1/3, colony stimulating factor receptor (CSF1R), RET, Abelson tyrosine kinase (Abl), and checkpoint kinase 2 (Chk2)}. It is not known if these in vitro kinase inhibitions translate into an effect in vivo. In combination with DNA-damaging agents (gemcitabine, topotecan, doxorubicin, and cisplatin), AZD-7762 inhibits tumour cell growth in vitro with a mode of action that correlates with Chk1 inhibition and abrogation of the Gap 2 (G2) and S phase checkpoints. Rightward shifts in 50% growth inhibition (GI50) values over DNA-damaging agents alone ranged from 5- to 20-fold with gemcitabine demonstrating the largest shifts followed by topotecan. In combination with radiation, AZD-7762 enhances tumour cell growth inhibition and death with survival enhancement ratios ranging from 1.7 to 1.9. Triple combinations with AZD-7762, gemcitabine, and radiation yield the largest survival enhancement ratios. AZD-7762 had been in phase I clinical trials by AstraZeneca for the treatment of solid tumors. However, this study was terminated for the safety reason in 2011.

Sameridine was developed as a compound with both local anesthetic and opioid properties (partial micro-opioid receptor agonist). This drug participated in clinical trials when administered intrathecally to provide anesthesia for surgery and extended postoperative analgesia. However, further development of this drug was discontinued.

Zibotentan (ZD4054) is a potent and specific orally available endothelin A (ETA) receptor antagonist, with no measurable affinity for endothelin B receptor. Activation of the ETA receptor by ET-1 has emerged as an important factor promoting tumor cell proliferation, survival, angiogenesis, migration, invasion, and metastasis in several tumor types. Zibotentan inhibits endothelin-mediated mechanisms that promote tumour cell proliferation. Zibotentan was being developed by AstraZeneca as treatment for heart failure, hormone resistant prostate cancer and other cancers including non-small cell lung, ovarian and breast cancer. However, following disappointing results from a phase III trial in patients with advanced prostate cancer, AstraZeneca decided to discontinue the development of zibotentan as a potential treatment for cancer. AstraZeneca undertook preclinical studies in the UK with zibotentan to investigate its potential as a treatment for heart failure. However, development for this indication has been discontinued.

Posizolid (AZD2563 or AZD5847) is an oxazolidinone, identified from an antibiotic research programme which aimed to synthesise agents that inhibited all Gram-positive bacteria, including multiresistant strains likely to be encountered clinically. Oxazolidinones bind to the 50S ribosomal subunit and inhibit the initiation phase of translation. Posizolid had been in phase II clinical trials for the treatment of tuberculosis. However, this study was discontinued.