Daniquidone, also known as Batracylin, is a water-insoluble heterocyclic amide with potential antineoplastic activity. Daniquidone inhibits topoisomerases I and II, thereby inhibiting DNA replication and repair, and RNA and protein synthesis. Batracylin advanced as an anticancer agent to Phase I clinical trials where dose limiting hemorrhagic cystitis (bladder inflammation and bleeding) was observed.

Peretinoin is an orally available, acyclic retinoid with potential antineoplastic and chemopreventive activities. Peretinoin binds to and activates nuclear retinoic acid receptors (RAR), which in turn recruit coactivator proteins and promote, with other transcriptional complexes, the transcription of target genes. As a result, this agent may modulate the expression of genes involved in the regulation of cell proliferation, cell differentiation, and apoptosis of both normal and tumor cells. Peretinoin inhibits post-therapeutic recurrence of hepatocellular carcinoma via unclear mechanisms. The European Commission granted Orphan Drug designation for Kowa's peretinoin to treat hepatocellular carcinoma (HCC).

3'-C-ethynylcytidine (Ethynylcytidine, TAS-106) is a synthetic cytidine nucleoside containing a covalently bound ethynyl group with potential antineoplastic and radiosensitizing activities. 3'-C-ethynylcytidine is metabolized in tumor cells to ethynylcytidine triphosphate (ECTP), which inhibits RNA synthesis by competitive inhibition of RNA polymerases I, II and III; subsequently, RNase L is activated, resulting in apoptosis. RNase L is a potent antiviral and antiproliferative endoribonuclease that cleaves singled stranded RNA, causes 28s rRNA fragmentation, and activates Janus Kinase (JAK), a mitochondrial-dependent apoptosis signaling molecule. Development of a cytosine derivative of 3'-ethynyl ribonucleoside, TAS-106, as an intravenously administered treatment for solid tumours was discontinued. A phase II trial in patients with head and neck cancer was terminated in the US.

Tallimustine (also known as FCE 24517), an alkylating benzoyl mustard derivative of distamycin A that was studied as an anti-tumor agent. Tallimustine participated in phase I clinical trial in patients with advanced cancer. As a result, the was obtained the recommended Phase II dosage for tallimustine. However, the further development of this drug was discontinued.

Pentamustine is an alkylating agent that was developed for the treatment of cancer. However, information about the further development of this compound is not available.

Geroquinol (geranylhydroquinone) is a radioprotective agent. It is also the major contact allergen of Phacelia Crenulate (a flowering plant in the borage family), which causes skin irritation comparable in degree to the skin reaction to urushiol, the sap found in poison oak/ivy. There is no cross-reaction with poison oak or ivy.

Tivantinib (ARQ 197) is the first non-ATP-competitive small molecule that selectively targets the c-Met receptor tyrosine kinase. Exposure to Tivantinib resulted in the inhibition of proliferation of c-Met-expressing cancer cell lines as well as the induction of caspase-dependent apoptosis in cell lines with constitutive c-Met activity. ArQule and its collaborators Daiichi Sankyo and Kyowa Hakko Kirin are developing tivantinib as a potential therapy for many cancers. c-Met is overexpressed in many cancers. Tivantinib currently is in phase 3 clinical development for the treatment of hepatocellular carcinoma and non-small cell lung cancer.

Indibulin is a novel synthetic compound that was identified in a cell-based screening assay to discover cytotoxic drugs. Indibulin destabilizes microtubules and blocks cell cycle transition specifically at the G2-M phase. Indibulin effectively induces apoptosis through Bcl-2 phosphorylation and Bax translocation in human malignant glioma cells in a p53-independent manner. This agent has been shown to be active against multidrug-resistant (MDR) and taxane-resistant tumour cell lines. Indibulin was used in phase I/II clinical trials of patients with advanced solid tumours (metastatic breast cancer). Pharmacokinetic analysis showed a better tolerability underfeeding condition. Dose-limiting toxicities were nausea and vomiting, which seemed to be related to solvent lactic acid.

Nortopixantrone (BBR-3438), a member of the 9-aza-anthrapyrazole family, is a DNA topoisomerase inhibitor potentially designed for the treatment of gastric cancer, ovarian cancer. BR 3438 exhibited a unique profile of preclinical activity with a superior efficacy against prostatic carcinoma models compared to reference compounds (doxorubicin and losoxantrone). Nortopixantrone had been in phase II clinical trials with Novuspharma for the treatment of gastric cancer, ovarian cancer and prostate cancer. But this research was discontinued in 2002.

Leurubicin was developed as a prodrug of doxorubicin (Dox) with the aim of lowering the cardiotoxicity and improving the therapeutic index produced by Dox. Antineoplastic agent Dox was rapidly formed from leurubicin, reaching peak levels in plasma within 5 min and in tissues within 1 h after i.v. administration of leurubicin. The incorporation of leurubicin into the MES-SA human uterine sarcoma cell line and its Dox resistant counterpart, MES-SA/Dx5 cell line and the subsequent transformation of leurubicin into Dox and its subcellular distribution, were investigated. In both cell lines the cellular uptakes of Dox and leurubicin were similar at equimolar doses, while the percent transformation of leurubicin into Dox in MES-SA/Dx5 cells was about twice as great as its transformation in MES-SA cells, which is beneficial for reaching Dox cytotoxic levels in this resistant cell line. The highest Dox/ leurubicin ratio was found in the nuclear fraction, followed by the ratio in the low density organelle fraction that contains lysosomes, organelles in which lysosomal hydrolytic enzymes, capthesins, transform leurubicin into Dox.