Taladegib (LY2940680) is an orally bioavailable small molecule antagonist of the Hedgehog (Hh)-ligand cell surface receptor smoothened (Smo) with potential antineoplastic activity. Taladegib inhibits signaling that is mediated by the Hh pathway protein Smo, which may result in a suppression of the Hh signaling pathway and may lead to the inhibition of the proliferation of tumor cells in which this pathway is abnormally activated. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair; constitutive activation of this pathway is associated with uncontrolled cellular proliferation and has been observed in a variety of cancers. Taladegib has excellent pharmacokinetic properties in rodent and non-rodent species. Taladegib administrated orally treats Ptch+/- p53-/- transgenic mice which spontaneously develop medulloblastoma, produces remarkable efficacy and significantly improves their survival. Taladegib reveals rapid kinetics of anti-tumor activity through magnetic resonance imaging of these mice, and Taladegib induces Caspase-3 activity and reduces proliferation by immunohistochemistry analysis of medulloblastoma tumors. Taladegib inhibits Hh regulated gene expression in the subcutaneous xenograft tumor stroma and produces significant anti-tumor activity. Taladegib is currently in phase I clinical trials for ovarian cancer and solid tumours and in phase I/II for esophageal cancer. Ignyta exclusively licensed Taladegib from Eli Lilly and Company in November 2015.

Zoliflodacin (also known as AZD0914 or ETX0914) is a spiropyrimidinetrione with activity against bacterial type II topoisomerases that inhibits DNA biosynthesis and results in accumulation of double-strand cleavages in bacteria. This drug is being a DNA gyrase inhibitor, targeting Neisseria gonorrhoeae and is currently in phase II clinical trial in adults to treat uncomplicated urogenital gonorrhea.

CHIR 99021 is a selective, pyridimidine-based, glycogen synthase kinase 3 inhibitor that is effective at low nanomolar concentrations in enzyme assays and submicromolar concentrations in isolated cells and tissues. Chiron was developing CHIR 99021 for potential use in the treatment of type 2 diabetes mellitus. CHIR 99021 promoted insulin-mediated glucose uptake and increased glucose disposal in rodent models of diabetes. However, there has been no recent development reported.

ARN-810 (GDC-0810) is a novel, orally bioavailable, estrogen receptor antagonist that induces proteasomal estrogen receptor degradation in breast cancer cell lines at picomolar concentrations and tumor regression in tamoxifen-sensitive and resistant BC xenograft models. Results from a first-in-human phase I/IIa study of ARN-810 indicate that it is tolerable and may benefit some postmenopausal women with advanced estrogen receptor-positive breast cancer. Development of ARN-810 was discontinued.

R-306465 is a sulfonyl-derivative patented by Janssen Pharmaceutica N.V. as class I histone deacetylase inhibitor with broad-spectrum antitumoral activity against solid and hematological malignancies. R-306465 rapidly induced histone 3 (H3) acetylation and strongly upregulated expression of p21waf1,cip1, a downstream component of HDAC1 signaling, in A2780 ovarian carcinoma cells. R306465 showed class I HDAC isotype selectivity as evidenced by poor inhibition of HDAC6 (class IIb) confirmed by the absence of downregulation of Hsp90 chaperone c-RAF protein expression and tubulin acetylation. R306465 potently inhibited cell proliferation of all main solid tumor indications, including ovarian, lung, colon, breast and prostate cancer cell lines. Hematological cell lines, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphoblastic leukemia, chronic myeloid leukemia, lymphoma, and myeloma, were potently inhibited at a similar concentration range. R306465 induced apoptosis and inhibited angiogenesis in cell-based assays and had potent oral in vivo antitumoral activity in xenograft models.

Icaritin is a monoprenylated favonol with 4′-methoxyl from Epimedium Genus. It has been documented to have osteoblastic and neuroprotective activities. It can reduce the incidence of steroid-associated oesteonecrosis in rabbit with inhibition of both intravascular thrombosis and extravascular lipid deposition for maintaining the integrity of intraosseous vasculature. Icaritin shows anti-infammatory activity and inhibitory activities against cancer cells. The phase III clinical trial is planned for the treatment of Hepatocellular carcinoma.

D-Fagomine (1,2-dideoxynojirimycin) is a six-membered ring iminocyclitol that was first isolated from seeds of buckwheat (Fagopyrum sculentum Moench, Polygonaceae) and is also present in other plant sources such as mulberry (Morus Alba, Moraceae) leaves and gogi (Lycium chinense) roots. D-fagomine is present in common buckwheat-based foodstuffs in amounts ranging from 1 to 25 mg/kg or mg/L, it is stable during boiling, baking, frying and fermentation, and it is biosynthesised upon sprouting. The estimated total intake of D-fagomine resulting from a diet that includes such foodstuffs would be between 3 and 17 mg per day (mean for both genders; range from P5 to P95). In animal studies D-Fagomine lowers postprandial blood glucose. D-fagomine agglutinated Enterobacteriaceae (Escherichia coli, Salmonella enterica serovar Typhimurium), while it did not show this effect on Bifidobacterium spp. or Lactobacillus spp. D-fagomine significantly inhibited the adhesion of Enterobacteriaceae and promoted the adhesion of Lactobacillus acidophilus to intestinal mucosa. D-Fagomine did not show any effect on bacterial cell viability. D-fagomine may be used as a dietary ingredient or functional food component to reduce the health risks associated with an excessive intake of fast-digestible carbohydrates, or an excess of potentially pathogenic bacteria.