MK-2048, diketo acid derivative, is a second-generation integrase strand transfer inhibitor (INSTI) developed to retain activity against HIV containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). MK-2048 implements its inhibitory mechanism by modifying viral integrase-DNA interactions, the important step of the linear HIV-1 cDNA integration into the host genome. It binds to and inactivates the synaptic complex, an intermediate in the concerted integration pathway in vitro thereby preventing target DNA binding and concerted integration. MK-2048 is active against viruses resistant to RAL and EVG. MK-2048 is equally potent against wild-type IN and raltegravir-resistant IN mutant N155H with a low IC50 value of 42 nM for inhibiting concerted integration. It inhibits R263K mutants slightly more effectively than G118R mutants. MK-2048 exposure leads to the selection of G118R as a possible novel resistance mutation.

Bristol-Myers Squibb was developing BMS 903452, a GPR119 agonist, for the treatment of patients with type 2 diabetes mellitus. G-protein-coupled receptor 119 (GPR119) is expressed predominantly in pancreatic β-cells and in enteroendocrine cells in the gastrointestinal tract. GPR119 agonists have been shown to stimulate glucose-dependent insulin release by direct action in the pancreas and to promote the secretion of the incretin GLP-1 by action in the gastrointestinal tract. BMS 903452 participated in phase I clinical trials in healthy subjects and in patients with type 2 diabetes mellitus to evaluate the safety, tolerability, and effect on blood glucose control. However, further information is not available.

Troxonium tosylate is a triethylcholine ester which resembles hemicholinium in some of its pharmacological effects. In animal pharmacological studies, it was noted that troxonium tosylate had a marked antitremorine activity with an associated hypotensive effect. This antitremorine activity, which is a common characteristic of antiparkinsonian agents, was found to be combined with an inhibitory function on acetylcholine synthesis and with a reduction of brain catecholamines. Troxonium tosylate was found to be an effective antiparkinsonian medication for drug-induced extrapyramidal manifestations. Troxonium tosylate caused a pronounced fall in the blood pressure in both normotensive and hypertensive animals. It produced this depressor effect mainly by antagonism of both central and peripheral autonomic ganglia. Troxonium did not possess atropine-like properties and was not active as an adrenergic blocker. Despite the potent effect upon the blood pressure, it did not significantly inhibit renal function and cardiac output. Because of its unique properties, it was postulated that troxonium might be of value in the management of hypertension of various etiologies.

Ambit Biosciences was developing AC-430, a potent inhibitor of Janus kinase 2 (JAK2) for the treatment of cancer and autoimmune diseases. AC-430 is a racemic mixture (50/50) of two enantiomers, AC410 and AC409. In preclinical studies, AC-430 has exhibited potency against JAK2 and V617F mutated JAK2 in cell-based models that is at least equivalent to, and in most cases superior to, competing JAK2 inhibitors. In preclinical oncology and autoimmune models, AC-430 is well tolerated and has significant efficacy at oral doses as low as 10 mg/kg/day.

AVL-3288 is a type I selective positive allosteric modulator of α7 nACHRs. It represents a "first-in-class" drug for the treatment of cognitive deficits in CNS disorders such as schizophrenia and potentially other diseases of cognitive impairment such as Alzheimer’s disease and ADHD. AVL-3288 was successfully tested in representative animal models of cognitive dysfunction in schizophrenia, a disease where α7 nAChR function is impaired. To date, no specific treatments for cognitive deficits in schizophrenia exist and approved therapies do not satisfactorily improve cognition. AVL-3288 is currently in human phase I trials.