Edelfosine is a synthetic alkyl-lysophospholipid, a potent immunomodulator and an effective inhibitor of tumor cell proliferation. The cytotoxic effect of edelfosine has been evaluated in a large variety of both tumor (leukemic and solid) and normal cell types, showing a high degree of selectivity towards tumor cells. Like all alkyl-lysophospholipids, Edelfosine incorporates into the cell membrane and does not target the DNA. In many tumor cells, Edelfosine causes selective apoptosis, sparing healthy cells. Edelfosine can activate the Fas/CD95cell death receptor, can inhibit the MAPK/ERK mitogenic pathway and the Akt/protein kinase B (PKB) survival pathway. Edelfosine apoptosis-inducing abilities were studied with several types of cancer, among them multiple myeloma and non-small and small cell lung carcinoma cell lines. In vivo activity against human solid tumors in mice was shown against malignant gynecological tumor cells, like ovarian cancer, and against breast cancer. In vivo biodistribution studies demonstrated a “considerably higher” accumulation of Edelfosine in tumor cells than in other analyzed organs. Several clinical trials were conducted. Among them, a phase I trials with solid tumors or leukemias and phase II with non-small-cell lung carcinomas (NSCLC). In Phase II clinical trial for use of Edelfosine in treating leukemia with bone marrow transplants, it was found to be safe and 'possibly effective'. A phase II trial for the treatment of brain cancers was also reported. It showed encouraging results in stopping the growth of the tumor and a considerable improvement in the “quality of life” of the patients. A phase II trial on the effect of Edelfosine on advanced non-small-cell bronchogenic carcinoma had a “remarkable” “high proportion of patients with stationary tumor status” as result, stable disease after initial progression in 50% of the patients.

BN-2629 (also known as SJG-136 and SG2000), a dimeric pyrrolobenzodiazepine that binds in the minor groove of DNA and produces G-G interstrand cross-links via reactive N(10)-C(11)/N(10')-C(ll') imine/carbinolamine moieties. This drug was investigated in phase II clinical trials in patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer, however, these studied were terminated because of the slow accrual. In addition, BN-2629 participated in phase I/II trial in participants with advanced chronic lymphocytic leukemia and acute myeloid leukemia, but Spirogen also terminated these studies.

Propizepine is a benzodiazepinone derivative patented by Laboratoires U.P.S.A. as antidepressive, antihistaminic, antianaphylactic, thymoanaleptic, antiserotonine, antispasmodic, and analgetic compound. Propizepine used in France for the treatment of depression in the 1970s.

KOS-1584 is a second-generation epothilone D analog designed to have less toxicity, more potency, and higher solubility compared with epothilone D. It has a broad spectrum of potent antiproliferative activity on tumor cells. Currently, KOS-1584 is under clinical evaluation.

Elsamitrucin is a heterocyclic antineoplastic antibiotic isolated from the bacterium Actinomycete strain J907-21. Elsamitrucin intercalates into DNA at guanine-cytosine (G-C)-rich sequences and inhibits topoisomerase I and II, resulting in single-strand breaks and inhibition of DNA replication. It demonstrated a broad spectrum of in vitro cytotoxicity against tumor cell lines. According to the results of Phase II trials elsamitrucin is not an active drug in patients with metastatic breast cancer, colorectal cancer, non-small cell lung cancer or ovarian cancer, however, it showed modest activity in patients with relapsed or refractory non-Hodgkin's lymphoma.

Piclamilast (RP 73401), is a selective PDE4 inhibitor. It is comparable to other PDE4 inhibitors for its anti-inflammatory effects. It has been investigated for its applications to the treatment of conditions such as asthma, dermatitis, rheumatoid arthritis. Emesis is the most commonly cited side effect of piclamilast.

Primycin is a topical antibiotic developed in Hungary for the local treatment of certain superficial and deep infections of the skin and subcutaneous tissue. Primycin is a complex of macrocyclic antibiotics comprising 20 compounds. Primycin possesses good in vitro activity against Staphylococcus aureus and coagulase-negative staphylococci, but its activity against Sirepiococctts pyogenes and enterococci is moderate. It is active against Micrococcus and Bacillus spp. but is inactive against Corynebacterium spp. It is inactive against Enterofojcterwceae and Pseudomonas aeruginosa, yeasts, and dermatophytes. The median lethal dose in the mouse is greater than 3,000 mg/kg of body weight orally and 56 mg/kg intraperitoneally. No skin lesions have been observed after chronic cutaneous applications (90 days) in the rabbit.

Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its condensation product, 3,3'-diindolylmethane (DIM) exert several biological activities on cellular and molecular levels, which contribute to their well-recognized chemoprevention potential. ndole-3-carbinol is used for prevention of breast cancer, colon cancer, and other types of cancer. The National Institutes of Health (NIH) has reviewed indole-3-carbinol as a possible cancer preventive agent and is now sponsoring clinical research for breast cancer prevention. Indole-3-carbinol is also used for fibromyalgia, tumors inside the voice box (laryngeal papillomatosis) caused by a virus, tumors inside the respiratory tract (respiratory papillomatosis) caused by a virus, abnormal cell growth in the cervix (cervical dysplasia), and systemic lupus erythematosus (SLE). Indole-3-carbinol scavenges free radicals and induces various hepatic cytochrome P450 monooxygenases. Specifically, this agent induces the hepatic monooxygenase cytochrome P4501A1 (CYP1A1), resulting in increased 2-hydroxylation of estrogens and increased production of the chemoprotective estrogen 2-hydroxyestrone. Accumulating evidence indicates that the antitumor activity of indole-3- carbinol is attributable to its ability to interfere with multiple oncogenic signaling pathways governing cell cycle progression, survival, invasion, and other aggressive phenotypes of cancer cells. Reported signaling targets of indole-3- carbinol in various cancer cell lines include EGFR/Src, Akt/NF-B, stress responses, elastase, and Rho kinase. Moreover, indole-3-carbinol functions as a negative regulator of estrogen action in hormonesensitive cancer cells through the inhibition of estrogen receptor (ER)-alpha signaling and/or induction of cytochrome P-450-mediated estrogen metabolism, suggesting its clinical use in hormone-sensitive cancers.

Ortataxel (previously known as IDN 5109 or BAY59-8862), a second-generation taxane derivative that was developed as an antitumor agent. Ortataxel binds to and stabilizes tubulin molecules, thereby interfering with the dynamics of microtubule assembly/disassembly. This results in the inhibition of cell division and cellular proliferation. In addition, ortataxel modulates multi-drug resistance mechanisms and may be useful for treating multi-drug resistant tumors that express Pgp, MRP-1, and BCRP. This drug participated in phase II clinical trials in patients with advanced renal cell carcinoma and in patients with Non-Hodgkin's lymphoma. However, these studies were discontinued. Ortataxel was also involved in phase II clinical trials for patients with glioblastoma; however, in a limited number of patients, the drug produced a benefit that lasted for a long time. Besides, ortataxel successfully completed phase II trials in taxane-resistant metastatic breast cancer patients and in taxane-resistant non-small cell lung cancer patients.

Saperconazole, a N-1-substituted triazole antifungal that is a selective inhibitor of the cytochrome P-450-dependent ergosterol synthesis in Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. Saperconazole participated in a clinical trial for the treatment of mycoses. However, further, development was discontinued because of concerns about the possibility of drug-induced carcinogenesis.