Fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU) is a thymidine nucleoside analog with activity against various herpesviruses and hepatitis B virus (HBV) in vitro and in vivo. Herpes virus thymidine kinase considered to be a target of FIAU. In a Phase II study, fialuridine induced a severe toxic reaction in chronic hepatitis B patients characterized by hepatic failure, lactic acidosis, pancreatitis, neuropathy, and myopathy. These clinical manifestations led to the hypothesis that the toxicity of FIAU was mediated through mitochondrial dysfunction, possibly as a result of the inhibition of mitochondrial DNA polymerase gamma and/or incorporation of FIAU into mitochondrial DNA.

IPI-549 is an orally bioavailable, highly selective small molecule inhibitor of the gamma isoform of phosphoinositide-3 kinase (PI3K-gamma) with potential immunomodulating and antineoplastic activities. Upon administration, IPI-549 prevents the activation of the PI3K-gamma-mediated signaling pathways, which may lead to a reduction in cellular proliferation in PI3K-gamma-expressing tumor cells. In addition, this agent is able to modulate anti-tumor immune responses and inhibit tumor-mediated immunosuppression. Unlike other isoforms of PI3K, the gamma isoform is overexpressed in certain tumor cell types and immune cells; its expression increases tumor cell proliferation and survival. By selectively targeting the gamma isoform, PI3K signaling in normal, non-neoplastic cells is minimally or not affected, which results in a reduced side effect profile. Preclinical data in multiple solid tumor models have demonstrated that IPI-549 targets immune cells and alters the immune-suppressive microenvironment, promoting an anti-tumor immune response that leads to tumor growth inhibition. A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing.

Elpamotide is an anti-angiogenic cancer vaccine. It is an HLA-A*24:02-restricted epitope peptide of vascular endothelial growth factor receptor 2 (VEGFR-2) (RFVPDGNRI) and induces cytotoxic T lymphocytes (CTLs) against VEGFR-2/KDR. OncoTherapy Science was developing elpamotide for the treatment of solid tumors.

Oxeclosporin (previously known as SDZ IMM 125 and now called as tigderimus) was developed as an immunosuppressive drug. It was shown that the drug possessed apoptotic activity via induction of uptake of extracellular calcium. The increased intracellular calcium might directly cause apoptosis by increasing the caspase-3 activity. Oxeclosporin was studied in clinical trials in patients with severe psoriasis. In addition, it was used for the treatment of rheumatoid arthritis and transplant rejection. However, all these studies were discontinued. Besides, oxeclosporin is participating in phase II trials in Europe for the treatment of asthma and in Switzerland for the treatment of cancer. However, information about the further development of this drug is not available.

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).

Ceralasertib, previously known as AZD6738, a potent and selective inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase was developed as an anticancer agent. Prevention of ATR-mediated signaling leads to the inhibition of DNA damage checkpoint activation, disruption of DNA damage repair, and the induction of tumor cell apoptosis. AZD6738 as a combination therapy participates in phase II clinical trials for the treatment of gastric adenocarcinoma and malignant melanoma (in combination with durvalumab). For the treatment of gastric and breast cancer in combination with carboplatin, or with olaparib or with MEDI4736. Combination of acalabrutinib and AZ6738 is used in phase II trials for patients with chronic lymphocytic Leukemia. Besides, AZD6738 participates in umbrella Phase II study in patients with metastatic non-small cell lung cancer (NSCLC) who have progressed on an anti-programmed cell death-1/anti-programmed cell death ligand 1 (anti-PD-1/PD-L1) containing therapy.

Vedotin fragment (Monomethyl auristatin E, MMAE; SGD-1010) is a synthetic derivative of dolastatin 10 and functions as a potent mitotic inhibitor by inhibiting tubulin polymerization. MMAE is widely used as a cytotoxic component of antibody-drug conjugates (ADCs) to treat several different cancer types. MMAE is a potent radiosensitizer. MMAE radiosensitization can be localized to tumors by targeted activatable cell-penetrating peptides.