2-Iminobiotin (2-IB) is a cyclic guanidino analog of biotin (Vitamin B7) and combined neuronal and inducible (but not endothelial) nitric oxide synthase inhibitor that has been demonstrated to improve neuroprotection in animal models of hypoxic-ischemic Brain Injury. While the exact mechanism of action has yet to be defined, 2-Iminobiotin potentially protects against hypoxic-ischemic brain damage by preventing nitric oxide or peroxynitrite-induced mitochondrial damage. In preclinical models, 2-Iminobiotin provides gender-specific neuroprotection against hypoxia-ischemia in neonatal rats by a NO-independent mechanism.

Tracazolate (ICI 136,753), a pyrazolopyridine, is a non-benzodiazepine with anxiolytic-like activity in animal models. It is known to interact with gamma-aminobutyric acid (GABA)(A) receptors, adenosine receptors, and phosphodiesterases. Its intrinsic efficacy, potentiation, or inhibition is determined by the nature of the third subunit (gamma1-3, delta, or epsilon) within the GABA(A) receptor complex.

Heidelberg Pharma Research developed fosalvudine tidoxil, a prodrug derived from the nucleoside reverse transcriptase inhibitor alovudine, for the treatment of HIV infections. This drug had reached phase II clinical trials before its development was discontinued.

Malethamer is the generic name of a new synthetic hydrocarbon copolymer with extraordinary water-binding properties, being able to absorb 200 times its weight of water. It is physically and chemically binds poliovirus 1 and certain bacterial enterotoxins. Ethylene-maleic anhydride copolymers and their derivatives have come to be considered for a number of applications generally involving the formation of insoluble complexes with proteins and viruses. The copolymer is not absorbed from the gastrointestinal tract and is pharmacologically inert. Malethamer, because of its water absorbing quality, is an effective compound for the symptomatic control of diarrhea, both organic and functional.

CHF-5074 is a small molecule with a unique microglial modulating mechanism of action capable of selectively reducing pro-inflammatory activities of microglial cells while increasing their ability to remove neurotoxic amyloid beta (“Aβ”) aggregates in the brain by phagocytosis. CHF-5074 reduces Aβ42 and Aβ40 secretion, with an IC50 of 3.6 and 18.4 μM, respectively. Microglia are small cells that migrate through the brain to remove waste products, such as amyloid aggregates that cause inflammation and irreversible damage to nerve cells. Chronic dysfunction of microglia is increasingly believed to play an important role at the very beginnings of Alzheimer’s disease. The results from Chiesi’s human clinical studies corroborate the large body of data from published preclinical studies. In Alzheimer’s disease transgenic mouse models, CHF-5074 was shown to reduce neuroinflammation, inhibit brain amyloid β plaque deposits, reduce tau pathology, and reverse associated memory deficits. These findings indicate CHF-5074 acts simultaneously on several important therapeutic targets, and this neuroprotective multi-target approach may translate into preventing the memory loss that is the hallmark of Alzheimer’s disease.

PF-04418948 is an orally active, potent, and selective EP2 receptor antagonist. It is used as a tool compound to study involvement of EP2 receptor in various pathologies. In combination with EP4 antagonist, PF-04418948 attenuates PGE2-induced airway microvascular leak in model of asthma, and PGE2-induced gut dismotility.