Trioxifene (LY133314) is a selective estrogen receptor modulator (SERM) with competitive binding activity against estradiol for estrogen receptor alpha (ERalpha) and antagonistic activity against ERalpha-mediated gene expression. Trioxifene has demonstrated activity in dimethyl-benzanthracene-induced mammary carcinoma in rats and human breast cancer patients. Trioxifene mesylate, an antiestrogen with a high FR affinity, was developed with the hope of improving the response rate of ER-positive patients, especially those with a borderline concentration of ER in their tumors. When used in vitro and in vivo, trioxifene has been shown to bind to the estradiol receptors with a binding affinity exceeding that of estradiol by a factor 1.7, whereas tamoxifen has a relative affinity of only 0.18 compared with trioxifene.

Navitoclax (ABT-263) is an oral selective inhibitor of B-cell leukemia 2 (Bcl-2) family of proteins with potential antineoplastic activity. Navitoclax is a small molecular with the formula of C47H55ClF3N5O6S3 and Molecular Weight of 974. As a Bad-like Bh3 minetic, ABT-263 binds to Bcl-2 family proteins Bcl-2, Bcl-xl and Bcl-w, disrupts the interaction between Bcl-2/Bcl-xl /Bcl-w and pro-apoptotic proteins such as Bim, Bad and Bak, which trigger the caspases-initiated cell death pathway to induce apoptosis. Navitoclax has been in phase II clinical trials by Abbvie for the treatment of prostate cancer, chronic lymphocytic leukaemia and lymphoma. However, this research has been discontinued.

Patupilone is a compound isolated from the myxobacterium Sorangium cellulosum. Similar to paclitaxel, Patupilone induces microtubule polymerization and stabilizes microtubules against depolymerization conditions. In addition to promoting tubulin polymerization and stabilization of microtubules, this agent is cytotoxic for cells overexpressing P-glycoprotein, a characteristic that distinguishes it from the taxanes. Epothilone B may cause complete cell-cycle arrest. Patupilone failed a phase III trial for ovarian cancer in 2010.

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.

Veribulin is a novel microtubule destabilizer that both functions as a potent cytotoxin and acts as a vascular disrupting agent (VDA). It binds to the same (or nearby) sites on β-tubulin as colchicine. It is capable of evading multidrug resistance pumps and, thus, achieves high CNS concentrations. It is efficacious in multiple xenograft models without CNS toxicity. Veribulin had previously demonstrated pre-clinical and clinical activity in multiple tumor types. Veribulin is in phase II clinical trial for the treatment of Glioblastoma and Malignant melanoma.

Acridine carboxamide (XR5000) is a tricyclic acridine-based (or carboxamide-based) drug with dual topoisomerase inhibitor and potential antineoplastic activities. Acridine carboxamide inhibits both topoisomerases I and II and intercalates into DNA, resulting in DNA damage, the disruption of DNA repair and replication, the inhibition of RNA and protein synthesis, and cell death. Acridine carboxamide has been used in trials studying the treatment of lung cancer and brain and central nervous system tumors. In clinical trials acridine carboxamide did not show efficacy when tested against various types of cancers.

Triciribine is a purine analogue which inhibits DNA and protein synthesis, it is a synthetic tricyclic nucleoside which acts as a specific inhibitor of the Akt signaling pathway. It selectively inhibits the phosphorylation and activation of Akt1, -2 and -3 but does not inhibit Akt kinase activity nor known upstream Akt activators such as PI 3-Kinase and PDK1. It inhibits cell growth and induces apoptosis preferentially in cells that express aberrant Akt1. In whole cells triciribine is phosphorylated by adenosine kinase which may be necessary for its activity. Triciribine is a cancer drug which was first synthesised in the 1970s and trialled clinically in the 1980s and 1990s without success. Following the discovery in the early 2000s that the drug would be effective against tumours with hyperactivated Akt, it is now again under consideration in a variety of cancers. As PTX-200, the drug is currently in two early stage clinical trials in breast cancer and ovarian cancer being conducted by the small molecule drug development company Prescient Therapeutics.

Tezacitabine is a cytidine derivative patented by Merrell Dow Pharmaceuticals, Inc. as an antineoplastic and antiviral agent. Tezacitabine acts as irreversible ribonucleotide reductase inhibitor and DNA chain terminator. Tezacitabine shows as potent activity in a broad spectrum of tumor cell lines and in vivo tumor models, including human colon, prostate, and breast tumor xenografts, In clinical trials combination of Tezacitabine and 5-Fluorouracil exerts favor influences in patients with advanced solid tumors particularly in patients with esophageal and other gastrointestinal carcinomas.

Steffimycin is a potent inhibitor of DNA dependent-RNA synthesis patented by Upjohn Co. as an antibiotic. Steffimycin interferes with amino acid incorporation mediated by synthetic polyribonucleotides in cell-free bacterial systems. This inhibition is a secondary activity of the antibiotic, which acts primarily as a suppressor of RNA synthesis in bacteria and bacterial cell-free systems. Inhibition of peptide biosynthesis is apparent only at a drug concentration higher than that necessary for inhibition of RNA synthesis in cell-free systems. In addition to antibiotic activity vs certain gram-positive organisms, Steffimycin inhibits the growth of KB cells and several fungi and shows antiviral activity against herpes simplex in mice

Uredepa, a thiotepa derivative, is a antineoplastic, alkylating agent. It has also been used experimentally as an insect chemosterilant.