Birinapant is a parenterally administered bivalent peptidomimetic of the SMAC protein (Second Mitochondria-derived Activator of Caspases) and is therefore known as a SMAC mimetic compound. Birinapant is a particularly potent antagonist of two members of the Inhibitor of Apoptosis Proteins (IAP) family, cIAP-1, and cIAP-2. cIAP-1 and -2 are ubiquitin ligases whose expression can protect cells from apoptosis and cause pro-survival effects of TNF-α and related ligands. When Birinapant binds to cIAP-1 or -2 it causes the protein to ubiquitinate itself, which in turn drives the degradation of the protein. In this way, birinapant suppresses the levels of cIAP-1 and cIAP-2 and therefore switches cell signaling to drive tumor cell apoptosis in the presence of TNF-α. Birinapant has been shown to give rise to sustained and substantial reductions of cIAP1 levels in Peripheral Blood Mononuclear Cells (PBMCs) and tumor tissue. To date, Birinapant has been dosed in approximately 450 patients across 9 studies. The majority of studies was in oncology (one in HBV) and primarily recruited patients with refractory solid tumors & hematological malignancies (dominated by ovarian, colorectal, acute myeloid leukemia and Myelodysplastic syndromes). Overall Birinapant has shown acceptable safety and tolerability for further development in oncology indications. The current plans are to study Birinapant clinically in combination with Keytruda® for the treatment solid tumors and in an Investigator-Initiated study at UCLA for high-grade serous carcinoma (HGSC) in combination with platinum-based chemotherapy.

Tiapamil (also known as Ro 11-1781) is a dithiane derivative patented by Hoffmann-La Roche, F., und Co., A.-G. as calcium-channel antagonist useful for myocardial infarction treatment. Tiapamil, like verapamil, inhibited in a concentration-dependent manner Ca2+-induced contractions in isolated, K+-depolarized preparations of rat renal artery, dog coronary artery and rabbit main pulmonary artery. The inhibitory effects of Tiapamil can be overcome by raising the Ca2+ concentration of the bath fluid. In the rabbit main pulmonary artery, Tiapamil reduces 45Ca influx into the K+-depolarized vascular smooth muscle cells. Tiapamil inhibits the slow potentials in partially depolarized guinea-pig papillary muscles. Tiapamil decreases contractile force in isolated guinea-pig atria and papillary muscles, as well as in isolated cat hearts. Tiapamil also reduces heart rate and increases coronary flow in these preparations. Tiapamil doubled coronary artery blood flow in the coronary sinus blood without producing major changes in blood pressure and heart rate in anesthetized dogs. Tiapamil did not affect contractions of isolated guinea-pig ileum, rat stomach strips or rat vas deferens in response to various stimulants. Tiapamil have no major effects on renal water and electrolyte excretion, on autonomic nerves and receptors, on pain perception and on the central nervous system. Acute, subacute, and chronic toxicity studies demonstrate low toxicity for Tiapamil with no tendency for accumulation. In clinical trials, Tiapamil effectively lowers systolic and diastolic blood pressure, but have no effects on heart rate

Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs). TTA exerts both hypolipidemic and anti-inflammatory effects in psoriasis patients - TTA can be of therapeutic benefit for a subgroup of psoriatic patients. TTA may improve myocardial function in heart failure, potentially involving its ability to decrease the availability of free fatty acids in plasma and increase the myocardial proportion of n-3 polyunsaturated fatty acids. TTA attenuates dyslipidemia in patients with type 2 diabetes mellitus. These effects may occur through mechanisms involving PPAR-alpha and PPAR-delta activation, resulting in increased mitochondrial fatty acid oxidation.

8-Azaguanine is a purine analog which resembles guanine close enough to compete with it in the metabolism of living organisms. It has been widely studied and has shown to cause retardation of some malignant neoplasms when administered to tumors in animals. It has been used for the treatment of patients with leukemia.

Chromanol is chromane derivative and o-tocopherol analog that has been used in trials studying the treatment of Prostate Cancer. Chromanol is potent water-soluble antioxidant and free radical scavenger. Chromanol inhibited overall oxidation of cis-Parinaric acid in phospholipids and protect cells to peroxyl radicals mediated NFkB activation and subsequent apoptosis. Chromanol inhibited the LPS-stimulated induction of NO production in a concentration-dependent fashion in cultured J774 macrophages and rat vascular smooth muscle cells without evidence of cytotoxicity.