RES-529 (previously named Palomid 529, P529) is a phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway inhibitor that interferes with the pathway through both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) dissociation. P529 inhibits tumor growth, angiogenesis, and vascular permeability. It retains the beneficial aspects of tumor vascular normalization that rapamycin boasts. This compound is currently being developed in oncology and ophthalmology. The oncology focus is for the treatment of glioblastoma, where it has received orphan designation by the US Food and Drug Administration, and prostate cancer.

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.

Phosphorylcholine (ChoP) is a small zwitterionic amino alcohol, which is composed of a negatively charged phosphate bonded to a small, positively charged choline group. Phosphorylcholine is the precursor metabolite of choline in the glycine, serine, and threonine metabolism pathways and in intermediate between choline and cytidine-diphosphate choline in the glycerophospholipid metabolism pathway. Phosphorylcholine is an interesting compound from an immunologic point of view, being an immunodominant determinant of pneumococcal teichoic acids and also a major prerequisite for proinflammatory effects of PAF and PAF-like lipids where PC is a common denominator. PC is also a component of some bacteria, apoptotic cells, and OxLDL, which, if exposed, is immunogenic. PC has several properties that could in principle both promote and protect against disease, depending on the pathogen and type of inflammatory reaction. In the field of interventional cardiology, phosphorylcholine is used as a synthetic polymer-based coating, applied to drug-eluting stents, to prevent the occurrence of coronary artery restenosis. To date, more than 120,000 Phosphorylcholine-coated stents have been implanted in patients with no apparent deleterious effect in the long term compared to bare metal stent technologies

Suricainide (also known as AHR 10718) is an aminoalkylurea derivative patented by A. H. Robins Co., Inc. as an antiarrhythmic agent. Suricainide induces a use-dependent decrease in Vmax and significantly decreased Purkinje fiber conduction velocity and action potential duration. Suricainide had no effect on slow response action potentials induced by isoproterenol but ventricular muscle action potentials were significantly prolonged by Suricainide. Suricainide significantly decreased normal automaticity, catecholamine-enhanced automaticity, and abnormal automaticity induced by barium or myocardial infarction. In preclinical modes, Suricainide suppresses the aconitine-induced canine atrial arrhythmia.

Zolertine is an alpha-adrenergic receptor antagonist that acts as an antihypertensive agent. Its effect was studied in animals in vivo and in vitro. Zolertine considerably decreased systemic blood pressure in mecamylamine hypertensive dogs in a dose-related fashion. Using the intravital microscopic method in rat's mesocygeus microvasculature a direct relationship between zolertine dosage and blockade was demonstrated as well as an inverse relationship between time of action of zolertine and percentage of vasoconstriction caused by noradrenaline. When only zolertine was applied, it caused a small vasoconstriction that decreased as its concentration increased which could be due to its ability to antagonize alpha receptor responses, but not beta responses. Zolertine is a more active alpha blocker than azapetin, a blocker used in medical practice. Competition binding experiments using the alpha1-adrenoceptor antagonist [3H] prazosin showed a zolertine pKi of 6.81 +/- 0.02 in rat liver (alpha1B-adrenoceptors) and 6.35 +/- 0.04 in rabbit liver (alpha1A-adrenoceptors) membranes. Zolertine showed higher affinity for alpha1D-adrenoceptors compared to alpha1A-adrenoceptors, while it had an intermediate affinity for alpha1B-adrenoceptors. The ability of the alpha1-adrenoceptor antagonist zolertine to block alpha1D-adrenoceptor-mediated constriction in different vessels of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats may explain its antihypertensive efficacy despite its low order of potency.

FLESINOXAN, a phenylpiperazine derivative, is a selective agonist for 5-HT1A receptors. It is an antidepressant agent which clinical development was stopped.

Pirolate is the pyrimidoquinoline. It was developed as an antiasthmatic and antiallergic agent. Pirolate does show high potency in passive cutaneous anaphylaxis in rats, both by intravenous and oral routes. It has some 84 times the potency of disodium cromoglycate. Pirolate is a leukotriene biosynthesis inhibitor.