AT-406 (DEBIO-1143, SM-406), is a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). AT-406 inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Debiopharm under a licence from Ascenta Therapeutics is developing AT-406 for the treatment of cancers.

Rubitecan [Orathecin™] is a topoisomerase I inhibitor extracted from the bark and leaves of the Camptotheca acuminata tree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. Rubitecan binds to and inhibits the enzyme topoisomerase I and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells; this agent also prevents repair of reversible single-strand DNA breaks.

AT-406 (DEBIO-1143, SM-406), is a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). AT-406 inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Debiopharm under a licence from Ascenta Therapeutics is developing AT-406 for the treatment of cancers.

D-Psicose (akaD-allulose) is a low energy monosaccharide found throughout nature in small quantities. t is a c-3 epimer of D-fructose and has 50% the sweetness of sucrose. Possible health benefits include improved insulin resistance, antioxidant enhancement and formation, and hypoglycemic controls. The use US-FDA lists psicose as generally recognized as safe (GRAS) and has approved its use as a food additive in a wide variety of products. Psicose is not generally metabolized and does not raise blood sugar levels above baseline after consumption. In addition, to use as a low-calorie sweetener, psicose has also been formally investigated as a dietary supplement to control obesity and pre-diabetic insulin insensitivities. Furthermore, D-psicose has shown the ability to inhibit the proliferation of ovarian cancer cells in vitro.

LY2606368 (Prexasertib) is a small-molecule Chk-1 inhibitors invented by Array and being developed by Eli Lilly and Company. Lilly is responsible for all clinical development and commercialization activities. LY2606368 is advancing in Phase 2 clinical trials for cancer. Prexasertib preferentially binds to and inhibits CHK1 and, to a lesser extent, inhibits CHK2. Chk-1 is a protein kinase that regulates the tumor cell's response to DNA damage often caused by treatment with chemotherapy. In response to DNA damage, Chk-1 blocks cell cycle progression in order to allow for repair of damaged DNA, thereby limiting the efficacy of chemotherapeutic agents. Inhibiting Chk-1 in combination with chemotherapy can enhance tumor cell death by preventing these cells from recovering from DNA damage.

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.

VX-970 (VE-822) is an ATR kinase inhibitor. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. Vertex Pharmaceuticals is developing VX 970 for the treatment of advanced solid tumours. Phase I/II development is underway in the US for small-cell lung cancer and in the UK for solid tumours. Phase II development of VX 970 as a combination therapy in urogenital cancer, ovarian, primary peritoneal and fallopian tube cancer indications is underway in the US.

LY2606368 (Prexasertib) is a small-molecule Chk-1 inhibitors invented by Array and being developed by Eli Lilly and Company. Lilly is responsible for all clinical development and commercialization activities. LY2606368 is advancing in Phase 2 clinical trials for cancer. Prexasertib preferentially binds to and inhibits CHK1 and, to a lesser extent, inhibits CHK2. Chk-1 is a protein kinase that regulates the tumor cell's response to DNA damage often caused by treatment with chemotherapy. In response to DNA damage, Chk-1 blocks cell cycle progression in order to allow for repair of damaged DNA, thereby limiting the efficacy of chemotherapeutic agents. Inhibiting Chk-1 in combination with chemotherapy can enhance tumor cell death by preventing these cells from recovering from DNA damage.

LY2606368 (Prexasertib) is a small-molecule Chk-1 inhibitors invented by Array and being developed by Eli Lilly and Company. Lilly is responsible for all clinical development and commercialization activities. LY2606368 is advancing in Phase 2 clinical trials for cancer. Prexasertib preferentially binds to and inhibits CHK1 and, to a lesser extent, inhibits CHK2. Chk-1 is a protein kinase that regulates the tumor cell's response to DNA damage often caused by treatment with chemotherapy. In response to DNA damage, Chk-1 blocks cell cycle progression in order to allow for repair of damaged DNA, thereby limiting the efficacy of chemotherapeutic agents. Inhibiting Chk-1 in combination with chemotherapy can enhance tumor cell death by preventing these cells from recovering from DNA damage.

Elesclomol (also known as STA-4783), originally identified in a cell-based phenotypic screen for pro-apoptotic activity, is a novel small-molecule that potently induces apoptosis of cancer cells through the rapid generation of reactive oxygen species (ROS) and the induction of unmanageable levels of oxidative stress. Elesclomol exhibits antitumor activity against a broad spectrum of types of cancer cell in human tumour xenograft models due to its excessive ROS production and elevated levels of oxidative stress leading to the death of cancer cells. Elesclomol is currently being studied as novel cancer therapeutic, in which it has demonstrated the ability to prolong progression-free survival in study subjects. Elesclomol induces oxidative stress by provoking a buildup of reactive oxygen species within cancer cells. Elesclomol requires a redox-active metal ion to function; the Cu(II) complex is 34 times more potent than the Ni(II) complex and 1040-fold more potent than the Pt(II) complex. Elesclomol is an HSP-90 Inhibitor with pro-apoptotic and potential antineoplastic activities. Elesclomol induces oxidative stress and triggers mitochondrial-induced apoptosis in cancer cells. Elesclomol is being developed by Synta Pharmaceuticals and GlaxoSmithKline as a chemotherapy adjuvant and has received both fast track and orphan drug status from the U.S. Food and Drug Administration for the treatment of metastatic melanoma. Synta Pharmaceuticals announced on February 26, 2009, the suspension of all clinical trials involving Elesclomol due to safety concerns. In March 2010, Synta announced that the FDA had approved resuming clinical development of elesclomol, and that they expected to initiate one or more clinical trials for elesclomol in the second half of the year. In a small, randomized phase II study, elesclomol was shown to significantly increase progression-free survival in people with metastatic melanoma when given in addition to paclitaxel (Taxol).