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.

Lomeguatrib is a O6-methylguanine-DNA-methyl-transferase inhibitor which was developed by AstraZeneca for the treatment of cancer. It was tested in phase I and II of clinical trials for the treatment of colorectal cancer, melanoma and other solid tumors.

Aphidicolin, a tetracyclic diterpenoid obtained from the culture filtrates of Cephalosporium aphidicola and other fungi, inhibits the growth of eukaryotic cells and of certain animal viruses (SV40, Herpes and Vaccinia viruses) by selectively inhibiting the cellular replicative DNA polymerase alpha or the viral-induced DNA polymerases. The arrest of cellular or viral growth is thus due to inhibition of cellular or viral replicative DNA synthesis without interference with mitochondrial DNA synthesis, RNA, protein and nucleic acid precursors synthesis or other major metabolic pathways. The inhibition of all sensitive eukaryotic DNA polymerases by aphidicolin is competitive with respect to dCTP. Aphidicolin has thus proved extremely useful in elucidating the functional role of DNA polymerase alpha in nuclear DNA replication, of DNA polymerase gamma in mitochondrial DNA synthesis and both DNA polymerases beta and alpha in DNA repair synthesis. An important laboratory application of aphidicolin is the synchronization of the cell cycle of eukaryotic cells both in culture and in vivo. The properties of aphidicolinhave recently aroused considerable interest for its possible exploitation in al practice. The mechanism of action of this drug suggests in fact that it may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.

AZD-5438 is an anti-cancer medicine which was developed by AstraZeneca. The drug is under development for the treatment of solid tumors in phase I of clinical trials. AZD-5438 exerts its anti-proliferative action both in vitro and in vivo by inhibiting cyclin-dependent kinases 1, 2 and 6 which are involved in the cell cycle.

AZD-1283 is an antagonist of P2Y12 receptor which was developed by AstraZeneca for the treatment of arterial thrombosis. The drug was tested in pre-clinical studies, however its develoment was terminated.

AZ5104 is a demethylated metabolite of Osimertinib. AZ5104 potently and irreversibly inhibits both wild-type and mutant (exon 19 and L858R) EGFR and demonstrates good anti-cancer effect in both cell-based and in vivo experiments. Although AZ5104 was tested on preclinical models of lung cancer, it is used only in the prodrug form.

AZ-1080 (AZD-1080) is an inhibitor of GSK-beta which was developed by AstraZeneca and initially tested in patients with Alzheimer’s disease (phase I). The drug was discontinued for the aforementioned condition, but now it is being investigated as a potential therapy for ovarina cancer and emdometrial carcinoma (basic research).

ZM 39923 HCl is an JAK1/3 inhibitor with pIC50 of 4.4/7.1 and almost no activity to JAK2 and modestly potent to EGFR. ZM39923 breaks down to form the JAK3 inhibitor ZM449829 which exhibit similar IC50 values. ZM39923 decomposes in neutral buffer to afford potent inhibition of the Janus kinase 3, and could be used as a standard Jak3 inhibitor in assays where breakdown could occur. ZM39923 is reduced by 300-fold in the presence of DTT (10 mM) in inhibiting TGM2. ZM39923 is reversible inhibitors when TGM2 is incubated with inhibitors in the absence of Ca2+. ZM39923 shows significant inhibition of crosslinking activity with IC50 of 25 nM in the absence of DTT and IC50 of 10 μM in the presence of DTT. ZM39923 prevents early death in a Drosophila Melanogaster model of a polyQ repeat disorder called Machado-Joseph Disease. M39923 inhibits the generation of AICD-FLAG and both Aβ40 and Aβ42 by purified γ-secretase in a concentration-dependent fashion with an approximate IC50 of 20 μM. ZM39923 decreases photoaffinity-labeled PS1-CTF in the presense of γ-secretase.