Alethine (Beta alethine) is an immunostimulant agent. It was undergoing clinical development with LifeTime Pharmaceuticals for the treatment of haematological malignancies. It is a low molecular weight disulfide that has been shown to exhibit in vivo antitumor activity in murine myeloma and melanoma models.

Xorphanol (also known as TR5379M) is a full κ-opioid receptor agonist and is a partial agonist at μ opioid receptor. Clinically, xorphanol was studied as an orally active analgesic that provided effective pain relief but showed low physical dependence liability. Further development of this drug was discontinued.

4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), a non-neurotoxic derivative of penclomidine, is under development by Dekk-Tec for the intravenous treatment of solid tumours. DM-CHOC-PEN is a cholesterol carbonate derivative of 4-demethylpenclomedine with potential antineoplastic alkylating activity. Upon intravenous administration of 4-demethylcholesteryloxycarbonylpenclomedine, the carbonium moiety binds to and alkylates DNA at the N7 guanine position, thereby causing DNA crosslinks. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. In addition, due to its lipophilic cholesteryl moiety this agent is able to cross the blood brain barrier (BBB) and therefore can be given intravenously compared to other alkylating agents that need to be given intra-cranially. DM-CHOC-PEN has undergone a Phase I study (allowed enrollment of subjects with advanced cancer +/- CNS involvement) and is being evaluated in a Phase II trial in subjects with advanced cancer involving the brain. DM-CHOC-PEN has completed Phase I/II trials in humans with primary and secondary tumors involving the brain with success. Complete remissions in both primary astrocytoma and metastatic lung and leukemia malignancies.Impressive objective responses and improved PFS/overall survival have been observed in subjects with NSCLC involving the CNS.

Swainsonine is an indolizidine alkaloid found in Australian Swainsona canescens, North American plants of the genera Astragalus and Oxytropis and also in the fungus Rhizoctonia leguminocola. It is competitive inhibitor of Golgi alpha-mannosidase II and lysosomal alpha-mannosidases. This compound has been reported to be a potent antiproliferative and immunomodulatory agent. However, no evidence of anti-tumor activity of swainsonine was seen in phase II clinical trial, in patients with locally advanced or metastatic renal cell carcinoma. Adverse events such as fatigue, nausea and diarrhea were common but generally mild. Swainsonine is locoweed toxin. Locoweed poisoning is seen throughout the world and annually costs the livestock industry millions of dollars. Swainsonine inhibits lysosomal alpha-mannosidase and Golgi mannosidase II. Poisoned animals are lethargic, anorexic, emaciated, and have neurologic signs that range from subtle apprehension to seizures.

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.

Squalamine is a steroid-polyamine conjugate compound with broad-spectrum antimicrobial activity and anti-angiogenic activity. Squalamine selectively inhibits new blood vessel formation; this activity is thought to be mediated through inhibition of the sodium-hydrogen antiporter sodium-proton exchangers (specifically the NHE3 isoform) causing inhibition of hydrogen ion efflux from endothelial cells, with subsequent reduction of cellular proliferation. Studies in tumor-bearing mice have shown that squalamine inhibits angiogenesis and tumor growth in xenograft models of lung, breast, ovarian, and prostate cancer and in brain and breast allograft tumor models in rats. Squalamine also has been shown to prevent lung metastases in the murine Lewis lung carcinoma model, both as a single agent and in combination with various other chemotherapeutics. Squalamine does not appear to have substantial direct effects on primary tumor growth in animal models when administered as a single agent. However, enhanced antitumor responses are observed when squalamine is administered in combination with cytotoxic chemotherapeutic agents when compared with cytotoxic agents used alone. Squalamine was studied as a potential cancer drug and as a potential treatment for wet macular degeneration but as of 2018 had not succeeded in Phase III trials for any use.

Enrasentan is an orally active mixed endothelin A/B receptor antagonist with a 100-fold greater affinity for the endothelin A receptor. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan had been in phase II clinical trial for the treatment of heart failure but the results suggested that enrasentan does not appear to have favorable effects on ventricular remodeling.

Afeletecan (Bay 38-3441) is a camptothecin glycoconjugate which stabilizes the active lactone form of camptothecin and allows selective uptake into tumor cells. Afeletecan is a topoisomerase inhibitor. Afeletecan was in phase I clinical trials with Bayer for the treatment of cancer; however, development appears to have been discontinued.