Carnosol is an ortho-diphenolic diterpene with an abietane carbon skeleton with hydroxyl groups at positions C-11 and C-12 and a lactone moiety across the B ring. Carnosol is the product of oxidative degradation of carnosic acid. Carnosol is a naturally occurring phytopolyphenol found in rosemary that functions as an antioxidant, antimicrobial, and anticarcinogen. Carnosol has been shown to inhibit inductions of COX-2 by blocking PKC signaling. Carnosol is an inhibitor of AR and ER α. Several pre-clinical studies have suggested that carnosol selectively targets tumorigenic cell as opposed to non-tumorigenic cells and is safe and tolerable in animals. Carnosol has been shown to elicit chemopreventive effects by (1) blocking the bioactivation of carcinogens, (2) enhancing antioxidant and/or detoxification enzyme activities, (3) suppressing tumor-promoting inflammation, (4) inhibiting cell proliferation and inducing apoptosis selectively in cancer cells, and (5) blocking tumor angiogenesis and invasion.

The immunosugar N-9-methoxynonyldeoxynojirimycin (SP-187, UV-4B) is an inhibitor of both glucosidases I and II. In preclinical studies, it displayed inhibition of dengue and influenza virus infection. The compound developed by Emergent BioSolutions and evaluated in phase 1 clinical trials on healthy subjects.

Trantelinium bromide is an anticholinergic and spasmolytic drug, used for the treatment of gastric ulcers.

PM-00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. PM-00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. Immunohistochemical studies in tumors also demonstrated histone-H2AX phosphorylation and p53 overexpression. PM-00104 has progressed into phase II clinical trials to treat Ewing sarcoma, urothelial carcinoma, multiple myeloma, endometrial and cervical cancer. The phase II study concluded that there were no objective responses in the cohort of 16 evaluable patients with Ewing sarcoma. The study of Urothelial carcinoma treatment was terminated early because there seemed to be no benefit from the current therapy. Moreover, PM-00104 as a single-agent did not prove to be an effective therapy for patients with advanced/metastatic endometrial or cervical cancer. None achieved objective tumor response was in phase II study for the treatment of advanced/metastatic endometrial or cervical cancer. Preliminary data showed PM-00104 to be safe to use in the treatment of multiple myeloma but the complete results from this trial have not been published.

TAK-960 is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor(IC50=1.5 nM) that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 had been in phase I clinical trials by Takeda for the treatment of solid tumours. It had also been in preclinical trials for the treatment of acute myeloid leukaemia. However, these studies were discontinued.

NB-001, an oil-in-water emulsion containing high energy nanometer-sized droplets stabilized by surfactants is designed for topical treatment of herpes labialis infections. NB-001 diffuses through the stratum corneum via the follicular route to accumulate in the epidermal and dermal tissues, without disrupting the normal epithelial matrix. The concentrations achieved in the epidermis and dermis are well above the concentrations required for antiviral activity.

Eprociclovir (A5021, 9-[[cis-1', 2'-bis(hydroxymethyl)cycloprop-1'-yl]methyl]guanine) is a nucleoside analog with antiviral activity. Antiviral activity of eprociclovir appears to depend rapid and stable accumulation of its triphosphate in infected cells and on inhibition of viral DNA polymerase by its triphosphate. Eprociclovir was shown to be a potent inhibitor of the replication of herpes simplex virus type 1, 2, 6, Epstein-Barr virus and varicella zoster virus, both in vitro and in vivo. Eprociclovir development has been discontinued.

Pfizer was developing PF-03814735, an orally administered, reversible inhibitor of the Aurora A and Aurora B kinases. In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1 (Thr 232, a sensitive marker of Aurora1 activity, with IC50 ~ 20 nM), phosphohistone H3 (with IC50 50 nM), and phospho-Aurora2 (with IC50 150 nM). PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells. A recent research indicates small cell lung cancer (SCLC) and, to a lesser extent, colon cancer lines are very sensitive to PF-03814735. The status of the Myc gene family and retinoblastoma pathway members significantly correlates with the efficacy of PF-03814735. PF-03814735 was under Phase I trials for patients with advanced solid tumors, but later this research was discontinued.