CAT-1004 (Edasalonexent)is an orally administered small molecule designed to inhibit NF-κB, which is activated from infancy in Duchenne muscular dystrophy and is central to causing muscle damage and preventing muscle regeneration. Structurally CAT-1004 represents covalently links salicylic acid and docosahexaenoic acid -- two compounds known to inhibit NF-κB. . In a Phase 1 study in adults, NF-κB activity in peripheral mononuclear cells was inhibited following a single dose of edasalonexent but not by equimolar doses of salicylic acid and docosahexaenoic acid. Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy, which occurs early in the disease process and precedes loss of muscle function. Salicylic acid prevents NF-κB mediated muscle atrophy and decreases protein catabolism in muscle. Docosahexaenoic acid has been shown to upregulate anti-inflammatory pathways and suppress pro-inflammatory pathways via modulation of NF-κB activity. Edasalonexent is endocytosed and hydrolyzed by intracellular fatty acid amide hydrolase (FAAH) to release salicylic acid and DHA in the intracellular compartment, thus having a potential advantage of selectively delivering higher doses in target muscle cells where FAAH is abundant.

(-)-Epigallocatechin is a polyphenol, which occurs naturally in various plants, including green tea leaves. The compound was shown to have anti-cancer activity in vitro, with breast cancer, lung cancer, and colon cancer cells. The commercial preparation of Polyphenon E contains about 3% (-)-epigallocatechin as an impurity.

Pevonedistat (MLN4924), discovered by Millennium, is a small molecule inhibitor of the NEDD8-Activating Enzyme (NAE), a key component of the protein homeostasis pathway. MLN4924 is a mechanism-based inhibitor of NAE and creates a covalent NEDD8-MLN4924 adduct catalyzed by the enzyme. The NEDD8-MLN4924 adduct resembles NEDD8 adenylate, the first intermediate in the NAE reaction cycle, but cannot be further utilized in subsequent intraenzyme reactions. The stability of the NEDD8-MLN4924 adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by MLN4924. This drug is in phase II clinical trial for the treatment acute myeloid leukemia, chronic myelomonocytic leukemia and myelodysplastic syndromes. In addition in phase I for treatment acute lymphoblastic leukemia. The ability of MLN4924 to cross the blood-brain barrier, its low toxicity, and clinical efficacy in other cancers suggests that this drug is an attractive treatment against glioblastomas.

Delanzomib (CEP-18770), a proteasome inhibitor, was being developed by Cepahlon (a subsidiary of Teva) for the treatment of cancer and immunological disorders. Delanzomib (CEP-18770) induces apoptotic cell death in multiple myeloma (MM) cell lines and in primary purified CD138-positive explant cultures from untreated and bortezomib-treated MM patients. In vitro, Delanzomib (CEP-18770) has a strong antiangiogenic activity and potently represses RANKL-induced osteoclastogenesis. Delanzomib represses the proteasomal degradation of a variety of proteins, including inhibitory kappaBalpha (IkappaBalpha), resulting in the cytoplasmic sequestration of the transcription factor NF-kappaB; inhibition of NF-kappaB nuclear translocation and transcriptional up-regulation of a variety of cell growth-promoting factors; and apoptotic cell death in susceptible tumor cell populations. In vitro studies indicate that this agent exhibits a favorable cytotoxicity profile toward normal human epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells relative to the proteasome inhibitor bortezomib. Delanzomib has been in phase II clinical trials for the treatment of multiple myeloma (MM). However, this research has been discontinued. Currently Delanzomib is on Phase I clinical trial for Non-Hodgkin's lymphoma and Solid tumours.

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor. urora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases, which have been shown to play important roles in the pathology of several cancers. ENMD-2076 is tested in phase 2 clinical trials against ovarian cancer, breast cance, hepatocellular carcinoma and other malignancies.

Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) is an organic compound mainly used as a broad spectrum, nonsystemic fungicide, with other uses as a wood protectant, pesticide, acaricide, and to control mold, mildew, bacteria, algae. Chlorothalonil reduces fungal intracellular glutathione molecules to alternate forms which cannot participate in essential enzymatic reactions, ultimately leading to cell death. Chlorothalonil is slightly toxic to mammals, but it can cause severe eye and skin irritation in certain formulations. Very high doses may cause a loss of muscle coordination, rapid breathing, nose bleeding, vomiting, and hyperactivity. Dermatitis, vaginal bleeding, bright yellow and/or bloody urine, and kidney tumors may also occur, followed by death. In a number of tests of varying lengths of time, rats which were fed a range of doses of chlorothalonil generally showed no effects on physical appearance, behavior, or survival. Kidney changes such as kidney enlargement were common. In the US, chlorothalonil is used predominantly on peanuts (about 34% of usage), potatoes (about 12%), and tomatoes (about 7%), though the EPA recognizes its use on many other crops. It is also used on golf courses and lawns (about 10%) and as a preservative additive in some paints (about 13%), resins, emulsions, and coatings. Chlorothalonil is commercially available in many different formulations and delivery methods. It is applied as a dust, dry or water-soluble grains, a wettable powder, a liquid spray, a fog, and a dip. It may be applied by hand, by ground sprayer, or by aircraft

PU-H71 is experimental inhibitor of Hsp90. It is being tested in clinical trials against lymphoma and solid tumors.

Thimerfonate is a alkyl mercuric derivative with germicidal activity.

APTO-253 is a novel small molecule that can induce expression of the genes that code for the Krüppel-like factor 4 (KLF4) master transcription factor and for the p21 cell cycle inhibitor protein, and can inhibit expression of the c-Myc oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. A Phase 1 study with APTO-253 was completed and demonstrated modest clinical activity in patients with colon cancer, acute leukemia, myelodysplastic syndrome, hematological malignancies and non-small cell lung cancers.

Annamycin is a highly lipophilic form of the anthracycline doxorubicin with the ability to bypass multidrug resistance mechanisms of cellular drug resistance. Annamycin belongs to the anthracycline class of drugs, and has a pleiotropic mechanism of action where it targets topoisomerase II, causing strand breaks in DNA. Annamycin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. The agent is being evaluated in separate phase 1 and phase 2 trials in the United States and Europe. Studies in animal models showed the agent to be noncardiotoxic. Trials that included patients with leukemia showed the agent was associated with fewer dose-limiting toxicities than typically experienced with doxorubicin. The FDA granted fast track designation to Annamycin for treatment of patients with relapsed or refractory acute myeloid leukemia.