Dibrospidium (Spyrobromin) is a dispirotripiperazine derivative and alkylating agent with potential antineoplastic and anti-inflammatory activities. The duration of DNA synthesis inhibition in tumor cells was found to correlate with spirobromine antitumor activity. Spirobromin is superior to prospidin by the power of the anti-inflammatory effect. Spyrobromin can diminish the latent period of the development of tumours in the experimental rats at intraperitoneal administration. At intragastric administration of the drug no decrease was noted in the latent period and no increase of tumours was observed in the experimental groups of the animals as compared with control. Dibrospidium has been examined for the treatment of bone cancer. The oral route of administration is the most safe with respect to the oncogenic risk. It was noted that spirobromin exerted the most pronounced toxic action on erythrocytes. Dibrospidium is used for the treatment of acute leukemias (mainly in combination therapy), malignant lymphomas, laryngeal cancer and skin reticulosis.

Evofosfamide, also formerly known as TH-302, is an investigational hypoxia-activated prodrug and is used to target cancerous cells under hypoxic conditions, which is a feature possessed by multiple solid tumors including glioblastoma and pancreatic cancer. Within regions of tumor hypoxia, evofosfamide releases bromo isophosphoramide mustard (Br-IPM), a potent DNA alkylating agent that kills tumor cells by forming DNA crosslinks. Once activated in hypoxic tissues, Br-IPM can also diffuse into surrounding oxygenated regions of the tumor and kill cells there via a “bystander effect”. Because of its preferential activation in the targeted hypoxic regions of solid tumors, evofosfamide may be less likely to produce broad systemic toxicity seen with untargeted cytotoxic chemotherapies.

Nemorubicin, a doxorubicin derivative, is a DNA-intercalator, topoisomerase and RNA synthesis inhibitor that was undergoing development with Nerviano Medical Sciences (Nerviano MS; formerly Pharmacia Italia) for the treatment of solid tumours, specifically, the loco-regional treatment of primary liver tumours (hepatocellular carcinoma). The drug is active on tumors resistant to alkylating agents, topoisomerase II inhibitors and platinum derivatives. It works primarily through topoisomerase I inhibition. Of note, Nemorubicin is active in cells with upregulation of the nucleotide excision repair (NER) pathway, where current therapies fail. Nemorubicin is biotransformed in the liver into cytotoxic metabolites that may further contribute to render this drug highly active against primary liver tumors or liver metastases. Clinical trials were conducted in Europe, US and China with Nemorubicin given at different dose-schedules and by different routes of administration: as single agent by systemic IV route, oral route and by intra-hepatic artery (IHA) infusion alone or in combination with cisplatin.

CNDAC (TAK-109) is an analog of the nucleoside deoxycytidine with potential antineoplastic activity. CNDAC is incorporated into DNA and induces single-strand breaks, which are converted into double-strand breaks (DSBs) when cells go through a second S phase. This results in the cell cycle arrest in the S and G2/M phases, DNA fragmentation, and tumor cell apoptosis. Sapacitabine, a prodrug of CNDAC, is being developed by the US biotechnology company Cyclacel for the treatment of hemalogical cancers and solid tumors.

Elinafide (LU 79553) is a bisintercalating naphthalamide and a topoisomerase II inhibitor has demonstrated a higher binding affinity for DNA and significant antitumour efficacy against a panel of established tumour cell lines, including several multidrug resistant-positive sublines. Elinafide had been in phase II clinical trial for the treatment of ovarian cancer and phase I trials for the treatment of various solid tumours. The major haematological toxicities observed were anaemia and neutropenia. The major non-haematological toxicities observed in the 3-weekly schedule were neuro-muscular presenting clinically as a mixed syndrome of severe weakness (sometimes with pain in both legs), myalgia and arthralgia, asthenia/fatigue/malaise. One fatality was considered related to LU 79553, as the patient had fever and neutropenia. Clinical study of this drug candidate was discontinued due to its neuromuscular dose-limiting toxicity.

Mafosfamide is a synthetic oxazaphosphorine derivative with antineoplastic properties. Mafosfamide alkylates DNA, forming DNA cross-links and inhibiting DNA synthesis. The effects of mafosfamide on various types of cancer cells were determined during preclinical investigations and clinical trials. Its development has been discontinued.

Ethidium is a DNA intercalating agent first discovered as and used as a veterenary trypanocide. A bromide salt is commonly used as a fluorescent tag in molecular biology. The fluorescene of ethidium bromide increased 21 fold upon binding to double-stranded RNA, 25 fold upon binding double stranded DNA. Because of the binding to DNA, ethidium bromide is a powerful inhibitor of DNA polymerase.

Chelerythrine is a kind of benzo[c] phenanthridine alkaloids, which is widely found in plant of Fumariaceae, Papaveraceae, Ranunculaceae and Rutaceae families. Chelerythrine is a potent and specific inhibitor of protein kinase C. In addition chelerythrine inhibits pro-survival protein Bcl(XL) thereby inducing apoptosis. It exerts antitumor properties.