Cryptotanshinone is one of the major tanshinones isolated from the roots of the plant Salvia miltiorrhiza Bunge (Danshen). Danshen has been widely used in traditional Chinese medicine for treatment of a variety of diseases, including coronary artery disease, acute ischemic stroke, hyperlipidemia, chronic renal failure, chronic hepatitis, and Alzheimer's disease, showing no serious adverse effects. Recent studies have shown that cryptotanshinone not only possesses the potential for treatment and prevention of the above-mentioned diseases, but also is a potent anticancer agent. In vitro studies have demonstrated that cryptotanshinone inhibits cell proliferation in a variety of cancer cell lines, including rhabdomyosarcoma, melanoma, cervical, colon, breast and prostate cancer cells. It has been described that cryptotanshinone induced a G1/G0 cell cycle arrest in rhabdomyosarcoma (Rh30) and prostate cancer (DU145) cells by downregulating expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb), but induced a G2/ M cell cycle arrest in melanoma (B16) cells via upregulating expression of Cdc25c, cyclin A1 and cyclin B1. Cryptotanshinone inhibiting expression of Aurora A kinase led to significant suppression of prostate cancer cells in vitro and in mice. Cryptotanshinone also induces cell death in cancer cells.

CCT241533, a 2-(quinazolin-2-yl)phenol compound, is an ATP competitive inhibitor of checkpoint kinase CHK2. CCT241533 blocked CHK2 activity in human tumor cell lines in response to DNA damage. CCT241533 significantly potentiates the cytotoxicity of PARP inhibitors. CCT241533 demonstrated a concentration dependent radioprotective effect in mouse thymocytes was demonstrated.

Pristimerin, the methyl ester of celasterol, is a triterpenoid quinone methide isolated from Pristimerae indica. Pristimerin shows anticancer activity in vitro towards myeloma, prostate, breast, ovarian cancer cell lines and inhibits xenografted plasmacytoma tumors in mice. In a rat model of adjuvant arthritis, pristimerin effectively inhibited both arthritic inflammation and cartilage and bone damage in the joints. Pristimerin acts by inhibiting NF-kB signaling pathway and the 26S proteasome.

Dioscin is a natural steroid saponin derived from several plants, showing the potent anti-cancer effect against a variety of tumor cell lines. Pharmacological studies have shown that dioscin processes anti-cerebral ischemia/reperfusion injury, anti-liver fibrosis and anti-obesity effects. Dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in prostate cancer cells. Dioscin remarkably suppressed the migratory and invasive capacities of melanoma cells. In preclinical models, dioscin showed significant anti-metastatic effects and suppress the tumor cell malignancy.

PIK-75 is a specific inhibitor of the p110 α isoform of phosphatidylinositol-3-kinase, an enzyme which is upregulated in several human cancers. PIK-75 is a p110α inhibitor with IC50 of 5.8 nM (200-fold more potently than p110β), it is also an inhibitor of CDK9. Cell-based assays revealed that PIK-75 potently and dose dependently inhibits in vitro and in vivo production of TNF-alpha and IL-6, diminishes the induced expression of human endothelial cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and blocks human monocyte-endothelial cell adhesion. Most importantly, PIK-75, when administered orally in a therapeutic regimen, significantly suppresses the macroscopic and histological abnormalities associated with dextran sulfate sodium-induced murine colitis. The efficacy of PIK-75 in attenuating experimental inflammation is mediated, at least in part, due to the downregulation of pertinent inflammatory mediators in the colon. Collectively, these results provide first evidence that PIK-75 possesses anti-inflammatory potential. Given that PIK-75 is known to exhibit anti-cancer activity, the findings from this study thus reinforce the cross-therapeutic functionality of potential drugs.

UNBS5162 is a naphthalimide that binds to DNA by intercalation and suppresses CXCL chemokine elaboration. In vivo and in vitro studies demonstrated potent antineoplastic properties of the compound. The phase 1 dose-escalation trial demonstrated that despite pre-clinical data suggesting low risk of QTc prolongation with UNBS5162 administration, there was a statistically significant relationship noted in study patients. The magnitude of QTc prolongation at the highest doses warranted the study drug to be terminated.

Veratramine, a steroidal alkaloid originating from Veratrum nigrum L. CYP2D6 and SULT2A1 mediating hydroxylation and sulfation were identified as the major biotransformation for veratramine. Veratramine significantly inhibits the hedgehog pathway in NIH/3T3 cells. Veratramine is both a release and uptake inhibitor of serotonin. Veratramine exhibits cytotoxic activity against human tumor cell lines A549, PANC-1, SW1990 and NCI-H249. Veratramine has demonstrated distinct anti-hypertension effects in spontaneously hypertensive rats.

Methyl chlorogenate, an antioxidant flavonoid, exhibited strong activity against HDAC8 and the high affinity to trichostatin A binding site. Methyl chlorogenate showed specific cytotoxicity against certain types of tested cancer cell lines such as Hep2 and MCF7. Methyl chlorogenate may inhibit NFkappaB activation, exhibiting its ability to downregulate the NFkappaB-dependent gene expression. Thus, it can be expected that Methyl chlorogenate may have potential for therapeutic intervention on various NFkappaB-dependent pathological conditions such as inflammatory or possibly mutagenic processes. Methyl chlorogenate has demonstrated antioxidant activity.

GW-4064 is a synthetic small molecule selective agonist of the orphan nuclear receptor FXR developed by GlaxoSmithKline. GW-4064-mediated FXR activation ameliorates diet-induced obesity, suppresses hepatic lipid accumulation, and maintains glucose and lipid homeostasis in C57BL/6 mice. GW-4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligand GW-4064 might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment.

Tetrahydro-4-Methylene-2-octyl-5-oxo-3-furancarboxylic acid or C75 is an inhibitor of fatty acid synthase. Additionally, C75 increased fatty acid oxidation and ATP levels by increasing carnitine palmitoyltransferase I (CPT I) activity. Unlike the activation produced by C75, the CoA derivative is a potent competitive inhibitor that binds tightly but reversibly to CPT I. C75 exerts antitumor and anti-obese potential. C75 has two enantiomers: (-)-C75 inhibits FAS activity in vitro and has a cytotoxic effect on tumor cell lines, without affecting food consumption, (+)-C75 inhibits CPT1 and its administration produces anorexia, suggesting that central inhibition of CPT1 is essential for the anorectic effect of C75.