Actein is tetracyclic triterpenoid compound isolated from the rhizome of Cimicifuga foetida L. In North America, the cimicifuga species had a long medicinal history, mainly used to treat diarrhea, sore throat, and rheumatism. Actein inhibits the activity of the Na,K-ATPase, which affects calcium metabolism. The primary target of actein may relate to calcium metabolism since this agent altered the expression of several genes related to calcium. Although actein was shown to exhibit other pathological functions, such as prevention of oxidative damage to osteoblast and regulation of lipid disorder, the major role of actein is played on its anticancer activity, particularly in breast cancer.

PQ401 is a diaryl urea compound and a potent inhibitor of autophosphorylation of the IGF-1 receptor. It has been investigated in preclinical studies as a potential cancer treatment in a number of cell models; most notably for breast cancer. It was also studied in mouse models as a possible treatment of diabetic neuropathies, although it showed less promise here.

CHIR-124 is a quinolone-based small molecule that is structurally unrelated to other known inhibitors of Chk1. CHIR-124 potently and selectively inhibits Chk1 in vitro. CHIR-124 interacts synergistically with topoisomerase poisons (e.g., camptothecin or SN-38) in causing growth inhibition in several p53-mutant solid tumor cell lines. CHIR-124 abrogates the SN-38-induced S and G(2)-M checkpoints and potentiates apoptosis in MDA-MD-435 breast cancer cells. CHIR-124 treatment can restore the level of cdc25A protein, which is normally targeted by Chk1 for degradation following DNA damage, indicating that Chk1 signaling is suppressed in the presence of CHIR-124. In an orthotopic breast cancer xenograft model, CHIR-124 potentiates the growth inhibitory effects of irinotecan by abrogating the G(2)-M checkpoint and increasing tumor apoptosis. The combination of gemcitabine and CHIR-124 in the multicellular tumor spheroid model enhanced the sensitivity to the gemcitabine antiproliferative effect in correlation with an increase in DNA damage and apoptosis. CHK1 inhibition by Chir-124 sensitizes HCT116 cancer cells to radiation.

16alpha-hydroxyestrone is a naturally occurring estrone metabolite. It exerts estrogenic properties through covalent estrogen receptor (ER) binding. 16alpha-hydroxyestrone is a potential tumor initiator. The ratio 2-hydroxyestrone to 16alpha-hydroxyestrone could serve as an innovative intermediate biomarker for breast cancer risk. This biomarker could be used to identify women at high risk, and provide the analytic framework for the development of new pharmaceutical and dietary intervention strategies.

SB-431542 was identified as a TGF-beta receptor type-1 inhibitor (IC50 = 94 nM) by scientists at GlaxoSmithKline. It has subsequently been studied in animal and cell models as a potential cancer treatment, although these efforts have been discontinued. Of note, SB-431542 was also used in a wound healing study where it was found to abolish the improved healing normally enhanced by treatment with Povidone-iodine.

Steviolbioside, 13-[(2-O-b-D-glucopyranosyl-b-D-glucopyrano syl)oxy]kaur-16-en-18-oic acid, is a bioactive nature sweetener, which is rare in Stevia rebaudiana leaves. It is also the main metabolite of the star sweetener rebaudioside A and its analogue stevioside, yet it can be used as an intermediate of some medications, which makes steviolbioside an important reagent in medical science in addition to a food additive. Steviolbioside has antituberculosis activity. Steviolbioside has been used in trials studying the treatment of HIV-1 Infection. Except for its antihyperglycaemic and antihypertensive effects, steviolbioside was found as a moderate antituberculosis activity against Mycobacterium tuberculosis strain H37RV in vitro (MIC = 3.75 ug/ml), compared to that of stevioside (MIC = 7.5 ug/ml). The hydrolysis product steviolbioside presented higher cytoxicity on human normal cells (hepatocytes cell L02 and intestinal epithelial cell T84) than did its starting material stevioside. e. Compared to the typical chemotherapy agent, 5-fluorouracil (5-FU), steviolbioside has a much lower cytotoxic effect on all assayed human normal cells, but it presented notable inhibition on Hep3B, human breast cancer cell MDA-MB-231 and human pancreatic cancer cell BxPC-3. The inhibition rate on MDA-MB-231 of steviolbioside was 50% of that of 5-FU, which implies a hopeful potential remedy for human breast cancer.

KI20227 is a potent and orally active inhibitor of c-Fms tyrosine kinase (M-CSFR, CSF1R) (IC50 values are 2, 12, 217 and 451 nM for c-Fms, VEGFR-2, PDGFRβ and c-Kit respectively). Ki20227 suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Ki20227 inhibits disease progression in a collagen-induced arthritis mouse model. Ki20227 suppresses experimental autoimmune encephalomyelitis. Ki20227 may be a useful therapeutic agent for osteolytic disease associated with bone metastasis and other bone diseases. Ki20227 and its derivatives may also be candidate drugs for the treatment of human multiple sclerosis. Ki20227 is currently in the preclinical developlent stage.

IN-1130 as a potent small molecule inhibitor of TGF-β signaling pathway. IN-1130 is a highly selective small molecule ALK5 inhibitor with >100 fold selectivity over p38α and a panel of 26 other serine/threonine and tyrosine kinases. It is a suppressor of fibrogenic process of unilateral ureteral obstruction in rats underscoring the potential clinical benefits in the treatment of renal fibrosis. IN-1130 may potentially treat prostate cancer and breast cancer (preclinical investigation phase).

L-fucose is a hexose deoxy sugar found on N-linked glycans on mammalian, insect and plant cell surfaces. Deficiency in L-fucose has been observed in several pathological conditions including cancer and atherosclerosis. On the other hand, L-fucose is an inhibitor of the sodium/myo-inositol transporter which may play a roll in the development of diabetes. L-fucose is has been considered as a diagnostic biomarker in several forms fo cancer.

PD 173074 is a potent ATP-competitive inhibitor of fibroblast growth factor receptor 1 and 3. PD173074 is also an effective inhibitor of FGFR2, FGFR4, and VEGFR2. Compared to FGFR1, PD173074 weakly inhibits the activities of Src, InsR, EGFR, PDGFR, MEK, and PKC with 1000-fold or greater IC50 values. PD173074 inhibits autophosphorylation of FGFR1 and VEGFR2 in a dose-dependent manner with IC50 of 1-5 nM and 100-200 nM, respectively. PD173074 specifically inhibits FGF-2-mediated effects on proliferation, differentiation, and MAPK activation in oligodendrocyte (OL) lineage cells. PD173074 treatment potently reduces the viability of FGFR3-expressing KMS11 and KMS18 cells. Inhibition of aFGF-stimulated MM cell growth by PD173074 is highly correlated with the expression of FGFR3. PD173074 treatment completely abolishes NIH 3T3 transformation mediated by Y373C FGFR3 but not by Ras V12, demonstrating that PD173074 specifically targets FGFR3-mediated cell transformation and lacks nonspecific cytotoxic effect. Administration of PD173074 at 1 mg/kg/day or 2 mg/kg/day in mice can effectively block angiogenesis induced by either FGF or VEGF in a dose-dependent manner with no apparent toxicity. PD173074 inhibits in vivo growth of mutant FGFR3-transfected NIH 3T3 cells in nude mice. Inhibition of FGFR3 by PD173074 delays tumor growth and increases survival of mice in a KMS11 xenograft myeloma model. In the H-510 xenograft, oral administration of PD173074 blocks tumor growth similar to that seen with single-agent cisplatin administration, increasing median survival compared with control sham-treated animals. In H-69 xenografts, PD173074 induces complete responses lasting >6 months in 50% of mice. These effects are correlated with increased apoptosis in excised tumors, but not a consequence of disrupted tumor vasculature. PD173074 seems to be discontinued in the preclinical development stage, and no clinical data are available currently.