Meisoindigo ((E)-1,1'-dimethyl-[3,3'-biindolinylidene]-2,2'-dione) is a derivative of Indigo Naturalis, that has been used in China for chronic myeloid leukemia. In vitro cell line studies have shown that this agent might induce apoptosis and myeloid differentiation of acute myeloid leukemia (AML). Meisoindigo has been a routine therapeutic agent in the clinical treatment of chronic myelogenous leukemia (CML) in China since the 1980s. In phase III clinical trial of Meisoindigo involving 402 patients, it was shown that Meisoindigo was equally efficient for both newly diagnosed and previously treated CML patients after oral administration. The hematological complete response (CR) and partial response (PR) rates, respectively, were 45.0 and 39.3% for newly diagnosed patients and 35.9 and 41.4% for previously treated patients. Meisoindigo was generally well tolerated. The most frequent side‑effects were bone, joint and/or muscle pain of varying degrees when the dosage was more than the suitable one.

Fostriecin, an antitumor antibiotic produced by Streptomyces pulveraceus, is a strong inhibitor of serine/threonine protein phosphatases type 2A and type 4, and inhibits the catalytic activity of partially purified Topo II (type II topoisomerase) in a non-competitive manner.

Avoralstat, a small molecule inhibitor of plasma kallikrein, participated in clinical trials phase III to prevent hereditary angioedema, but these studied were discontinued due to insufficient efficacy study. Recently published article has described that avoralstat could improve the quality of life in C1‐INH‐HAE patients. Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1‐INH‐HAE) is an autosomal dominant disorder characterized by recurrent episodes of swelling of the skin, pharynx, gastrointestinal tract, genitals, and is due primarily to mutations in the SERPING1 gene that results in insufficient production of the natural plasma kallikrein inhibitor, C1 inhibitor (C1‐INH).

Tideglusib (NP031112, NP-12, Nypta, Noscira SA, Madrid, Spain), a drug, which belongs to the thiadiazolidinone family, is a GSK-3β inhibitor. Tideglusib was in phase II clinical trials for the treatment of Alzheimer disease (AD) and progressive supranuclear palsy. Participants showed no benefit on either of the primary outcome measures or exploratory endpoints and further development in the drug was halted for these two disease. However, Tideglusib is on phase II clinical trial to determine whether drug is safe and efficacious in the treatment of adolescents and adults with congenital and juvenile-onset Myotonic Dystrophy.

Volasertib (BI 6727), a dihydropteridinone derivative, is a small-molecule cell cycle inhibitor of polo-like kinase-1 (PLK-1). Volasertib induces G2-M arrest and induction of apoptosis in cancer cells and potently inhibits tumor growth in xenograft models. Boehringer Ingelheim is developing intravenously administered volasertib for the treatment of acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML), non-small cell lung cancer, urogenital cancer, ovarian cancer and solid tumours.

Dofequidar (MS-209), a quinolone-derived sphingomyelin synthase inhibitor that blocks P-glycoprotein and multidrug resistance-associated protein-1, is under development by Schering for the potential treatment of multidrug resistant tumors. MS-209 had been in phase III clinical trials for the treatment of breast cancer and non-small lung cancer. But this research was discontinued in 2004. Detected adverse events are: nausea, vomiting, leukopenia, neutropenia, anorexia, constipation.

1-(2-DEOXY-2-FLUORO-β-D-ARABINOFURANOSYL)URACIL (FAU) is a thymidine analog. In several cancer cell lines, FAU was phosphorylated intracellularly to its monophosphate, 1-(2-deoxy-2-fluoro--Darabinofuranosyl) uracil monophosphate (FAUMP), by thymidine kinase and methylated in the 5-position by thymidylate synthase to form the product, 1-(2-deoxy-2-fluoro- -D-arabinofuranosyl) 5-methyluracil monophosphate (FMAUMP). FAU strongly inhibits the growth of tumor cells with high thymidylate synthase activity. FAU had been in phase I clinical trial for the treatment of advanced solid tumors.

Arno Therapeutics is developing AR-12, an orally available, targeted therapy for cancer and infectious diseases. AR-12 is a potentially first-in-class, orally available, targeted anti-cancer agent that has been shown in preclinical studies to inhibit phosphoinositide-dependent protein kinase-1, or PDK-1, a protein in the PI3K/Akt pathway that is involved in the growth and proliferation of cells, including cancer cells. Although FDA-approved drugs that target the Akt pathway have shown efficacy in treating cancer, some tumors either do not respond to these drugs or eventually become resistant to therapy. Scientists hypothesize that a combination of drugs that inhibit different targets in this pathway could provide synergistic or additive benefits to increase efficacy and potentially overcome drug resistance. For this reason, there has been particular interest within the biopharmaceutical industry in developing inhibitors of PI3K, PDK-1, and Akt. AR-12 was licensed to Arno in January 2008 by The Ohio State University Research Foundation for commercial development by Arno as a potential treatment for solid tumors and hematological malignancies. In preclinical studies, AR-12 has shown efficacy in a wide range of tumor types, including breast, lung, prostate, pancreatic, brain and hematological cancers, as both a single-agent as well as in combination with leading oncology therapeutics. Also AR-12 represents a promising class of small molecules with broad-spectrum antifungal activity. AR-12 inhibits fungal acetyl coenzyme A (acetyl-CoA) synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma. AR-12 has a broad spectrum of activity, including activity against yeasts (e.g., Candida albicans, non-albicans Candida spp., Cryptococcus neoformans), molds (e.g., Fusarium, Mucor), and dimorphic fungi (Blastomyces, Histoplasma, and Coccidioides) with MICs of 2 to 4 ug/ml. AR-12 is also active against azole- and echinocandin-resistant Candida isolates, and subinhibitory AR-12 concentrations increase the susceptibility of fluconazole- and echinocandin-resistant Candida isolates. Also AR-12 acts as a broad-specificity anti-viral drug in vitro and in vivo. AR-12 (OSU-03012) interacts with multiple chaperone proteins of the HSP90 family and the HSP70 family resulting in a broad spectrum of chaperone inactivation. This overall loss of chaperone functionality results in cells being more readily capable of undergoing autophagic processes and in cells that have a reduced competency for virus replication.

Pracinostat is a pan-histone deacetylase inhibitor being tested in phase II of clinical trials for the treatment of sarcoma, prostate cancer, acute myeloid leukemia, myelofibrosis, myelodysplastic syndrome. The drug was shown to be active in vitro on HCT116 and HL-60 cells.

AGE-RELATED MACULAR DEGENERATION (AMD), PROLIFERATIVE DIABETIC RETINOPATHY (PDR) AND DIABETIC MACULAR EDEMA (DME) are collectively characterized by VEGF mediated retinal leakage, angiogenesis, and an underlying inflammatory process. TargeGen's TG100801 is designed to inhibit a select group of kinases involved in those three processes. Currently approved drug based therapy for macular degeneration requires repeated injection into the eye. TG100801 is the first topically applied, VEGFR)/Src kinase inhibitor to advance into the clinic for the treatment of Age-related macular degeneration, diabetic retinopathy. The formation of new blood vessels (angiogenesis), blood vessel leakage, and inflammation contribute to the progression of the eye disease, which is the leading cause of irreversible, severe loss of vision in people 55 years of age and older in the developed world. In cell based assays, following topical instillation, TG100572, the active drug produced by conversion of TG100801 as it penetrates the eye, was shown to induce apoptosis in proliferating endothelial cells responsible for neovasculariztion and to inhibit inflammatory-mediated processes as measured by endotoxin-induced nitric oxide release in vitro.