Antineoplaston A10 is a piperidinedione antineoplaston with potential antineoplastic activity. Antineoplaston A10 was originally isolated from human urine but is now synthetically derived. This agent intercalates into DNA, resulting in cell cycle arrest in G1 phase, reduction of mitosis, and decreased protein synthesis. Antineoplaston A10 may also inhibit ras-oncogene expression and activate tumor suppressor gene p53, leading to cell differentiation and apoptosis. Antineoplaston A10 has been used in trials studying the treatment of glioma, sarcoma, lymphoma, lung cancer, liver cancer, and kidney cancer, among others.

Porfiromycin is an N-methyl derivative of the antineoplastic antibiotic mitomycin-C initially isolated from Streptomyces ardus. Upon administration, the drug undergoes chemical or enzymatic reduction, followed by spontaneous loss of the tertiary methoxy (hydroxyl) group and formation of an aromatic indole system. Thus activated, porfiromycin generates oxygen radicals and alkylates DNA, producing interstrand cross-links and single-strand breaks at guanosine residues. Porfiromycin was tested in phase III for head and neck carcinoma, however, its development was terminated.

Streptonigrin is an antibiotic produced by Streptomyces flocculus. Streptonigrin exhibits activity as a broad spectrum antibiotic against both Gram-positive and Gram-negative bacteria. Streptonigrin shows antitumor activity against sarcomas, carcinomas, leukemias and lymphomas in vivo and in vitro. Due to its high toxicity, streptonigrin has not recieved widespread clinical use.

Amonafide L-malate (AS1413, Xanafide) is a DNA intercalator and topoisomerase II inhibitor that induces apoptosis by disrupting chromatin organisation independently of ATP. This is different from classical topoisomerase II inhibitors which induce apoptosis by causing extensive DNA damage. Amonafide L-malate is also able to evade P-glycoprotein and related transporters that contribute to multi-drug resistance. AS1413 had orphan drug status in both the U.S. and the E.U. for the treatment of AML and also received Fast Track status from the U.S. FDA for the treatment of secondary AML. Amonafide L-malate was originated by Xanthus Pharmaceuticals. It was added to Antisoma's pipeline through the acquisition of Xanthus Pharmaceuticals, Inc. in June 2008. Antisoma discontinued development of Amonafide L-malate after data from the open-label, international Phase III ACCEDE trial in over 420 patients showed that 600 mg/m 2 IV amonafide for 5 days plus cytarabine missed the primary endpoint of significantly improving initial remission rate, defined as the proportion of patients who achieve CR or CRi, vs. daunorubicin plus cytarabine.

Benzodepa is an aziridine alkylating agent that cross-links with DNA, causing inhibition of DNA synthesis. It has been studied as a potential treatment for a variety of cancers, most notably bronchiogenic carcinoma.

Arenobufagin, a representative natural bufadienolide compound, is the major active component extracted from toad venom. Arenobufagin is a part of Chinese medicine Chan'su. It possesses significant antineoplastic activity in vitro. Antineoplastic activity of arenobufagin was tested using cell lines from different cancers: breast cancer, hepatocellular carcinoma, prostatic cancer, etc. Arenobufagin acts by intercalating with DNA and disrupting the cell cycle. Also it was shown to inhibit PI3K/Akt/mTOR pathway (in hepatocellular carcinoma cells) and inhibit Na, K-ATPase.