2-Methoxyestradiol (2ME2) is a natural metabolite of endogenous estrogen hormone 17β-estradiol in human and devoid of estrogenic activity. It is a drug that prevents the formation of new blood vessels that tumors need in order to grow (angiogenesis). It has undergone Phase 1 clinical trials against breast cancers. Preclinical models also suggest that 2ME2 could also be effective against inflammatory diseases such as rheumatoid arthritis. 2-Methoxyestradiol is an angiogenesis inhibitor, and has been shown to attack both tumor cells and their blood supply in preclinical testing. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. 2-Methoxyestradiol shows strong cytotoxic effect on estrogen dependent and independent cancerous cells, which is mainly due to disruption of microtubule process and p53 induced apoptosis through caspase, reactive oxygen species (ROS), superoxide dismutase (SOD) and nitric oxide synthase. 2-Methoxyestradiol inhibits tubulin polymerisation by binding to colchicine binding site of the tubulin and arrests cell cycle at G2/M-phase.

Rostaporfin (SnET2, Purlytin, REM-001), a second generation photosensitizer drug, that was developed as part of Miravant's PhotoPoint photodynamic therapy (PDT) program, for the potential treatment of wet age-related macular degeneration (AMD). It was found a red light with a wavelength of 664 nm activated the drug. It is injected into the patient, where it distributed and selectively bound to plasma lipoproteins, which were produced in high concentrations by hyperproliferating cells such as cancer cells. In January 2002, results of phase III trials indicated that rostaporfin had not met the primary efficacy endpoint for the wet form of AMD. In addition, rostaporfin has been studied in phase 2 and/or Phase 3 clinical trials in cutaneous metastatic breast cancer (CMBC). It was shown that the drug was able to reduce or eliminate a substantial number of treated CMBC tumors. On March 1, 2018, Adgero Biopharmaceuticals Holdings, Inc. announced that the U.S. Food and Drug Administration (“FDA”) has granted Orphan Drug Designation to REM-001 (rostaporfin), for the treatment of Basal Cell Carcinoma Nevus Syndrome (“BCCNS”). BCCNS is a rare but serious condition with few available therapies and many patients lack treatment options.

Tesetaxel is a taxane derivative patented by Daiichi Pharmaceutical Co., Ltd. as antitumor agent. Preclinical research suggests that tesetaxel may overcome P-glycoprotein-mediated multidrug resistance, thereby facilitating extended intracellular retention and possibly clinical effectiveness. Tesetaxel exhibited potent cytotoxicity against various human and murine cancer cell lines and was particularly potent against cell lines expressing P-glycoprotein. Orally administered tesetaxel showed potent in vivo antitumor activity in murine syngeneic and human xenograft models. The cytotoxic effect of tesetaxel, unlike that of other taxanes, was not influenced by the level of P-glycoprotein expression or by the presence of a P-glycoprotein modulator. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies.

Ammonium trichlorotellurate (AS-101) is a synthetic non-toxic tellurium derivative, structurally similar to cisplatin, with immunostimulatory and anti-hair loss properties. Ammonium trichlorotellurate induces production of colony stimulating factor (CSF), interleukin-2 (IL-2), and IL-2 receptors by increasing the calcium ion influx through the cell membrane and subsequently exerts its immunostimulatory effects through the CSF-mediated increase in macrophage/granulocytes. This agent is also a potent inducer of interferon and a spectrum of cytokines such as IL-1, IL-6, and tumor necrosis factor (TNF). In animal studies, ammonium trichlorotellurate exerts its anti-hair loss effect by inducing anagen and obstructing spontaneous catagen via promoting follicular keratinocyte proliferation and interfering with terminal differentiation, respectively. AS-101 suppresses production of HIV-1. It inhibited reverse transcriptase activity and replication of human immunodeficiency virus type 1. RDDP and DDDP activities were impaired by the drug with calculated IC50 value of about 4 uM. Intravenous AS-101 was in trials in patients with HIV infections. AS-101, a small-molecule integrin αvβ3 and VLA-4 inhibitor is being developed by BioMAS in Israel for the treatment of genital warts, age-related macular degeneration and fertility preservation. Phase II clinical trials are ongoing. The drug was also undergoing phase II development in acute myeloid leukaemia, atopic dermatitis, chemotherapy-induced damage, myelodysplastic syndromes, thrombocytopenia, alopecia, psoriasis. However, development for these indications was discontinued.

Tariquidar, a non-competitive, specific P-glycoprotein (Pgp) inhibitor, is an anthranilamide derivative with multidrug resistance properties. Tariquidar binds to the ATP-binding cassette (ABC) transport protein Pgp, thereby inhibiting transmembrane transport of anticancer drugs resulting in their increased intracellular concentrations augmenting cytotoxicity of an anticancer drug. Tariquidar was discovered by Xenova Group and was developed for the treatment of multidrug resistance in cancer. In October 2002 the US Food and Drug Administration (FDA) has granted fast track review status to tariquidar for the treatment of multi-drug resistance in first-line treatment of non-small cell lung cancer (NSCLC) patients. Tariquidar is still undergoing research as an adjuvant against multidrug resistance in cancer.

Filanesib is a highly selective, targeted KSP inhibitor with a mechanism of action distinct from currently available myeloma therapies such as immunomodulatory drugs (IMiDs®) and proteasome inhibitors. Across multiple studies, filanesib has demonstrated activity in heavily pretreated multiple myeloma patients, with a consistent safety profile including no drug-induced peripheral neuropathy and limited non-hematologic toxicity. Adverse events are generally limited to transient, non-cumulative and predominantly asymptomatic myelosuppression (decreases in blood counts) when supportive measures are used. Alpha 1-acid glycoprotein (AAG), a plasma protein, is a potential patient selection marker for filanesib. AAG is undergoing further investigation in clinical trials and could represent the first patient selection marker for a myeloma therapy. Filanesib is in Phase II for Multiple myeloma treatment.

Tanespimycin (17-allylamino-17-demethoxygeldanamycin, 17-AAG) is a synthetic analogue of geldanamycin, an antibiotic first purified in 1970 from Streptomyces hygroscopicus. Tanespimycin is an Hsp90 inhibitor that has demonstrated the potential to disrupt the activity of multiple oncogenes and cell signaling pathways implicated in tumor growth, including HER2, a key pathway in breast cancer. Tanespimycin was being under development by Kosan Biosciences. It was in phase 3 clinical development with bortezomib for the treatment of multiple myeloma (MM). However, in 2010 the company halted development of tanespimycin, during late-stage clinical trials as a potential treatment for multiple myeloma. While no definitive explanation was given, it has been suggested that Bristol-Myers Squibb halted development over concerns of the financial feasibility of tanespimycin development given the 2014 expiry of the patent on this compound, and the relative expense of manufacture.

CPG-52852 (PF-04878691) is a toll-like receptor 7 (TRL7) agonist. The drug was developed by 3M Pharmaceuticals and the Coley Pharmaceutical Group and was investigated in a number of clinical trials in patients with advanced cancer. Sustained tolerability and modest clinical benefit were demonstrated in heavily pretreated recurrent breast, ovarian, and cervix cancers. After Coley was acquired by Pfizer in 2007, the drug was repurposed for the treatment of hepatitis C. A phase 1 clinical trial was conducted. The development of the compound was discontinued because the compound was believed to unlikely to achieve the proof-of-concept criteria as a result of pharmacodynamic modeling.