CEP-32496 (RXDX 105) is an orally administered, small molecule, VEGFRsparing, RET, BRAF, EGFR tyrosine kinase inhibitor, for the treatment of solid tumours, including malignant melanoma and colorectal cancer. CEP-32496 was originally discovered by Ambit Biosciences (now Daiichi Sankyo) and Cephalon (now owned by Teva) as part of a research programme to develop orally administered kinase inhibitors. The worldwide rights to the compound were licensed to Teva by Ambit, following the acquisition of Cephalon by Teva. Teva, in March 2015, entered into an asset purchase agreement with Ignyta, pursuant to which, Ignyta has acquired worldwide rights and assets of four oncology development programmes, including CEP-32496. Following the acquisition of the compound by Ignyta, CEP 32496 has been renamed to RXDX 105. Phase I/Ib development of RXDX 105 for the treatment of advanced solid tumours is underway in the US.

Teroxirone is a triazene triepoxide patented by Shell Internationale Research Maatschappij NV as an antineoplastic agent. Teroxirone alkylates and cross-links DNA, thereby inhibiting DNA replication. Teroxirone has good cytotoxic activity against sublines of P388 and L1210 leukemias resistant to another alkylating agent. In preclinical trials, Teroxirone shows potent antineoplastic activity against murine tumors. In clinical trials, Teroxirone shows good anticancer activity and high rate of adverse events including nausea, vomiting, and myelosuppression.

Vatalanib a potent oral tyrosine kinase inhibitor with a selective range of molecular targets, has been extensively investigated and has shown promising results in patients with solid tumors in early trials. Vatalanib selectively inhibits the tyrosine kinase domains of vascular endothelial growth factor (VEGF) receptor tyrosine kinases (important enzymes in the formation of new blood vessels that contribute to tumor growth and metastasis), platelet-derived growth factor (PDGF) receptor, and c-KIT. The adverse effects of vatalanib appear similar to those of other VEGF inhibitors. In the CONFIRM trials, the most common side effects were high blood pressure, gastrointestinal upset (diarrhea, nausea, and vomiting), fatigue, and dizziness.

Panomifene (also known as GYKI-13504 or EGIS-5660), a triphenyl-alkene derivative that was studied as an antiestrogen. This drug binds to specific estrogen receptors and exhibits inhibitory effects on experimental mammary tumors both in vitro and in vivo. Panomifene reached phase II clinical trials for the treatment of breast cancer before development was terminated.

Intoplicine is a pyrido[4,3-b]indole derivative patented by Rhone-Poulenc Sante as an antitumor agent. Intoplicine acts via inhibiting DNA nicking and closing reactions by stabilizing the cleavable complex, a transient intermediate in the religation reaction involving topoisomerase I and II and DNA. Intoplicine was active in a range of solid tumors in mice, including colon adenocarcinoma 51, MA16/C, MA14/A, MA13/C, early-stage pancreatic ductal adenocarcinoma 03, Glasgow osteogenic sarcoma and B16 melanoma. In Phase I clinical studies using a 24-h infusion, the maximum tolerated dose was established as 270 mg/m2 every 3 weeks, with hepatotoxicity rather than myelosuppression being dose-limiting, although cardiac toxicity was also seen. Preclinical cytotoxic concentrations were not achieved at the dose levels studied and clinical development was discontinued.

Esorubicin (4'-deoxydoxorubicin, NSC 267469) is a synthetic derivative of the anthracycline antineoplastic antibiotic doxorubicin with potential antineoplastic activity. Esorubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. This agent exhibits less cardiotoxicity than the parent antibiotic doxorubicin, but may cause more severe myelosupression compared to other compounds within the anthracycline class. Esorubicin was being clinically tested for the treatment of solid tumors as well as lymphomas an leukemias. Esorubicin development has been discontinued.

Detorubicin is a semi-synthetic derivative of the anthracycline antineoplastic antibiotic. It intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. This agent also produces toxic free-radical intermediates and interacts with cell membrane lipids causing lipid peroxidation. Detorubicin is less toxic than daunorubicin. Although it showed some clinical activity, the drug appeared to have no particular advantage over doxorubicin except for demonstrated activity against malignant melanoma. Unfortunately, detorubicin clearly has cardiac toxicity – in clinical trial, one patient developed congestive heart failure and other patients revealed endomyocardial biopsy evidence of cardiac toxicity.

Berubicin, an anthracycline derivative, is a DNA binding agent and potent topoisomerase II poison. Reata Pharmaceuticals were developing it as a treatment for brain cancer as it can breach the blood-brain barrier. It had also been in early clinical trials for the treatment of lung cancer and malignant gliomas. However, studies have been terminated. In October 2006, it was granted orphan drug designation from the FDA for the treatment of malignant gliomas. According to a CNS Pharmaceuticals media release in April 2018, berubicin will be studied for glioblastoma patients, these investigations will be funded in part by an equity crowdfunding campaign.

Bofumustine, also known as RFCNU was studied as an antitumor agent. Bofumustine participated in phase II trials in patients with digestive tract tumors. It was shown that 30% has remissions among which 13% were greater than 50%. In addition, bofumustine participated in phase II clinical trials, where it showed to be effective in 8% of digestive tumors, in 1 out of 7 pancreatic cancers and in 3 out of 10 hepatic and pulmonary metastases from an undiscovered primary adenocarcinoma. However, further information is not available.

Sarcolysin is the isomeric form of melphalan with alkylating activity. Sarcolysin is a bifunctional alkylating agent. The cytotoxicity of sarcolysin appears to be related to the extent of its interstrand cross-linking with DNA, probably by binding at the N7 position of guanine. Like other bifunctional alkylating agents, it is active against both resting and rapidly dividing tumor cells. The levo-isomer - melphalan (L-sarcolysin) is approved under the brand name ALKERAN for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. In addition, the drug was approved under the trade name Evomela. Evomela is indicated for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma. In addition, for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.