FG 2216 is an erythropoietic small molecule prolyl hydroxylase inhibitor, originally developed by FibroGen, that is undergoing development for the treatment of anemia. PDH inhibitor FG-2216 was orally bioavailable and induced significant and reversible EPO induction in vivo. Chronic oral dosing in male rhesus macaques was well tolerated, significantly increased erythropoiesis, and prevented anemia induced by weekly phlebotomy. Furthermore, modest increases in HbF-containing red cells and reticulocytes were demonstrated by flow cytometry. FG 2216 had been in phase II clinical trials for the treatment of anemia, however, all researchers on this drug candidate were discontinued.

Nelociguat, a soluble guanylate cyclase (sGC) activator, has been in phase II clinical trials by Bayer for the treatment of erectile dysfunction and heart failure. However, no recent development has been reported. Nelociguat is a direct soluble guanylate cyclase (sGC) stimulator that acts independently of nitric oxide (NO); has an EC50 of 353 nM on P-VASP formation in rat aortic smooth muscle cells. BAY 60-4552 is pharmacologically active major metabolite of Riociguat.

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.

Indolapril (CI-907) is a new orally active prodrug of nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, developed by Warner-Lambert/Parke-Davis Pharmaceutical Research for treating hypertension. Indolapril is epimer of trandolapril, well-known ACE inhibitor currently in the market for hypertension treatment. Indolapril (Monoester form) and it’s active component (diacid form) produced concentration related ACE inhibition in guinea-pig serum (IC50 for monoester -- 0.1 mkM and for diacid -- 2.6 nM). In isolated rabbit aortic rings and in rat and dog autonomic studies, Indolapril is highly specific in suppressing the contractile or pressor responses to angiotensin I. In two-kidney, one-clip Goldblatt hypertensive rats, single daily doses (0.03-30 mg/kg p.o.) produced dose-dependent decreases in blood pressure; 3 mg/kg lowered blood pressure to normotensive levels. In the spontaneously hypertensive rat, subacute administration of Indolapril produced the same decrease in blood pressure as that obtained in the renal hypertensive rat. In diuretic-pretreated renal hypertensive dogs, 10 mg/kg normalized blood pressure. For equivalent drops in blood pressure, heart rate increases were less in Indolapril than in enalapril-treated renal hypertensive dogs. No side effects were observed with CI-907 in any of the conscious animals. The antihypertensive response to Indolapril (0.03-1.0 mg/kg p.o.) was found to correlate with inhibition of vascular tissue ACE, but not plasma or brain ACE in two-kidney, one-clip renal hypertensive rats.

Flosfluridine tidoxil, a thymidylate synthase inhibitor that was developed for the treatment of actinic keratosis and solid tumors, e.g. breast and colorectal cancers. These studies were suspended and information about the further development of this drug is not available.

Dasolampanel (NGX-426) is an orally available competitive antagonist of the AMPA and kainate receptors. The dug originated at Eli Lilly and Horizon Pharma and was developed for the treatment of migraine and neuropathic pain. Dasalompanel was reduced capsaicin-induced pain and hyperalgesia in human volunteers but failed to achieve positive results in phase 2 clinical trials in patients with pain due to osteoarthritis of the knee and diabetic peripheral neuropathic pain.

Besifovir (also known as LB80331), an active metabolite of LB80380 was studied for the treatment of hepatitis B.

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