7Z-Calcipotriol is an isomeric impurity in vitamin D analog calcipotriol. Synthesis of 7Z-Calcipotriol was disclosed by Japanese company Kuraray Co in a patent application JP 06316558.

TIC10 (TIC10 isomer or ONC201 isomer) is a potent, orally active, and stable small molecule and is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The isomeric structure of TIC10/ONC201 is critical to its activity: anti-cancer activity is associated with the angular structure and not the linear TIC10 isomer. TIC10 transcriptionally induces a sustained up-regulation TRAIL in tumors and normal cells in a p53-independent manner. TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 crosses the blood-brain barrier. TIC10 treatment caused tumor regression in the HCT116 p53−/− xenograft, RKO human colon cancer xenograft–bearing mice and human triple-negative breast cancer xenografts and significantly prolonged the survival of Eμ-myc transgenic mice, which spontaneously develop metastatic lymphoma from weeks 9 to 12 of age by 4 weeks.

LY-3039478 is an orally bioavailable, novel small molecule inhibitor of Notch signaling pathway, developed Eli Lilly and Company for cancer treatment. The Notch receptor, on the surfaces of progenitor cells and cancer cells, binds neighboring cell-surface ligands DLL or JAGGED. On ligand binding, the intramembrane protease γ-secretase cleaves the Notch intracellular domain (NICD). LY-3039478 is an exquisitely potent inhibitor of Notch-1 intracellular domain (N1ICD) cleavage with an IC50 of ∼1nM in most of the tumor cell lines tested. LY3039478 also potently inhibits mutant Notch receptor activity. Treatment with a gamma-secretase inhibitor, LY3039478, significantly inhibited the growth of 2 CCRCC(Clear cell renal cell carcinoma) cell lines in a concentration-dependent manner. LY3039478 treatment also led to decreased expression of Myc and Cyclin A1, two genes that were part of the NOTCH driven proliferative signature in murine and human model systems. LY3039478 treatment also led to G0/G1 cell cycle arrest in CCRCC cells. In a xenograft tumor model, LY3039478 inhibited N1ICD cleavage and expression of Notch-regulated genes in the tumor microenvironment. The inhibition of Notch cleavage also resulted in the induction of apoptosis in a Notch-dependent xenograft model. In immunodeficient NSG mice xenografted with 769-P CCRCC cells, LY3039478 treatment resulted in significantly increased survival and delayed tumor growth in independent cohorts of mice demonstrating in vivo efficacy in CCRCC. LY3039478 is being investigated in a clinical trial in patients with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma in combination with Dexamethasone.

Pterostilbene is a naturally derived compound found primarily in blueberries and Pterocarpus marsupium heartwood. The multiple benefits of pterostilbene in the treatment and prevention of human disease have been attributed to its antioxidant, anti-inflammatory, and anti-carcinogenic properties leading to improved function of normal cells and inhibition of malignant cells. The antioxidant activity of pterostilbene has been implicated in anti-carcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. Pterostilbene increases LDL and reduces blood pressure in adults. Low doses of pterostilbene seem to hold some benefit for cognition.

MLN8054 is a reversible, ATP competitive inhibitor of recombinant Aurora A, developed by Millennium Pharmaceuticals. MLN8054 was tested in phase I clinical trials against advanced solid tumors. Reversible somnolence probably due to off-target inhibition of alpha-1 subunit of GABA-A receptor was dose limiting and prevented achievement of plasma concentrations predicted necessary for target modulation.

PF-3758309 was developed as an ATP-competitive inhibitor of PAK4. In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50 = 1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50 = 4.7 nM). PF-3758309 blocks the growth of multiple human tumor xenografts, with a plasma EC50 value of 0.4 nM in the most sensitive model. PF-3758309 is antiproliferative and induces apoptosis in an HCT116 tumor model.

APTO-253 is a novel small molecule that can induce expression of the genes that code for the Krüppel-like factor 4 (KLF4) master transcription factor and for the p21 cell cycle inhibitor protein, and can inhibit expression of the c-Myc oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. A Phase 1 study with APTO-253 was completed and demonstrated modest clinical activity in patients with colon cancer, acute leukemia, myelodysplastic syndrome, hematological malignancies and non-small cell lung cancers.

10-Hydroxycamptothecin (10-HCPT), an indole alkaloid isolated from a Chinese tree, Camptotheca acuminate, inhibits the activity of topoisomerase I and has a broad spectrum of anticancer activity in vitro and in vivo. However, its use has been limited due to its water-insolubility and toxicity with i.v. administration. Prolonged elimination of 10-HCPT in vivo may have a significant impact on its therapeutic effects. 10-HCPT is metabolized to its carboxylate form and glucuronides.It was investigated that relatively low dose of 10-HCPT is able to inhibit the growth of colon cancer, facilitating the development of a new protocol of human trials with this anticancer drug.

Emodin is a naturally occurring anthraquinone present in the roots of numerous plants and lichens and an active ingredient of various Chinese herbs. Emodin possesses various biological properties and serves as an anti-bacterial and anti-inflammatory agent. Emodin was studied as a potential anti-cancer agent: e.g., it was shown, that compound inhibits the invasion and migration of colon cancer cells in vitro and in vivo by blocking EMT, which is related with the inhibition of Wnt/β-catenin signaling pathway. Besides, emodin effectively ameliorates asthmatic airway inflammation and alternatively activated macrophages (AAMs) polarization, and thus can be a potential agent for the treatment of asthma. It is known that the Inhibition of AAMs is an alternative therapeutic strategy for treating asthma. Some experiments have revealed that emodin can be a beneficial dietary supplement in prolonging lifespan.

SAR-020106 is an ATP-competitive, potent, and selective inhibitor of CHK1, a serine/threonine kinase associated with DNA damage-linked S and G(2)-M checkpoint control. SAR-020106 is a potent radio- and chemosensitizer in tumor cell lines and in vivo xenograft models.