CG-200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed by CrystalGenomics, Inc for treatment of various hematological and solid cancers. Combinations of CG-200745 with SN38 (the active form of irinotecan), or oxaliplatin were more effective than the agents alone when used to inhibit the growth of HCT116 cells. The protein expressions of acetyl-H3, p21, caspase-3, -8, and -9, PARP, and XIAP were affected in a time- and dose-dependent manner in HCT116 cells treated with the CG-200745 alone or combined CG-200745 and SN-38. In HCT116 xenografts, the HDACI CG-200745 in combination with irinotecan dramatically inhibited tumor growth without showing additive toxicity.

Fluorocyclopentenylcytosine (RX-3117) is a novel small molecule nucleoside compound that is incorporated into DNA or RNA of cancer cells and inhibits both DNA and RNA synthesis which induces apoptotic cell death of tumor cells. Fluorocyclopentenylcytosine also mediates the down-regulation of DNA methyltransferase 1 (DNMT1), an enzyme responsible for the methylation of cytosine residues on newly synthesized DNA and also a target for anticancer therapies. Preclinical studies have shown Fluorocyclopentenylcytosine to be effective in both inhibiting the growth of various human cancer xenograft models, including colon, lung, renal and pancreas, as well as overcoming chemotherapeutic drug resistance. Fluorocyclopentenylcytosine has demonstrated a broad spectrum anti-tumor activity against 50 different human cancer cell lines and efficacy in 12 different mouse xenograft models. The efficacy in the mouse xenograft models was superior to that of gemcitabine. In addition, in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine, Fluorocyclopentenylcytosine still retains its full anti-tumor activity. In August 2012, Rexahn reported the completion of an exploratory Phase I clinical trial of Fluorocyclopentenylcytosine in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of Fluorocyclopentenylcytosine demonstrated an oral bioavailability of 34-58% and a plasma half-life (T1/2) of 14 hours. In addition, Fluorocyclopentenylcytosine was safe and well tolerated in all subjects throughout the dose range tested. Fluorocyclopentenylcytosine is in phase I/II clinical trials by Rexahn for the treatment of bladder cancer and pancreatic cancer. This compound was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pancreatic cancer in September 2014.

NLG919 is a novel small-molecule IDO-pathway inhibitor. NLG919 potently inhibits this pathway in vitro and in cell-based assays. It is orally bioavailable and has a favorable pharmacokinetic and toxicity profile. In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ∼ 50%. Using IDO-expressing human monocyte-derived DCs in allogeneic MLR reactions, NLG919 potently blocked IDO-induced T cell suppression and restored robust T cell responses with an ED50=80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro. In vivo, in mice bearing large established B16F10 tumors, administration of NLG919 markedly enhanced the anti-tumor responses of naïve, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA

Levdobutamine is a beta-adrenoceptor agonist selective for the beta1-subtype. Levdobutamine was derived from dopamine. It is the active (S)-isomer of dobutamine. It is the cardiotonic agent.

Triciribine is a purine analogue which inhibits DNA and protein synthesis, it is a synthetic tricyclic nucleoside which acts as a specific inhibitor of the Akt signaling pathway. It selectively inhibits the phosphorylation and activation of Akt1, -2 and -3 but does not inhibit Akt kinase activity nor known upstream Akt activators such as PI 3-Kinase and PDK1. It inhibits cell growth and induces apoptosis preferentially in cells that express aberrant Akt1. In whole cells triciribine is phosphorylated by adenosine kinase which may be necessary for its activity. Triciribine is a cancer drug which was first synthesised in the 1970s and trialled clinically in the 1980s and 1990s without success. Following the discovery in the early 2000s that the drug would be effective against tumours with hyperactivated Akt, it is now again under consideration in a variety of cancers. As PTX-200, the drug is currently in two early stage clinical trials in breast cancer and ovarian cancer being conducted by the small molecule drug development company Prescient Therapeutics.