Animal experiment:

Rats[2]Rats are fasted for 16 hours prior to use. At the beginning of the experiment, each rat is weighed, and then anesthetized using 5% isoflurane for induction and 2.5% for maintenance. A blood sample from tail vein is collected for a fasting blood glucose determination using a standard glucometer. Rats are then given an intraperitoneal (i.p.) injection of DPCPX (3 mg/kg, n=4), ABT-702 (3 mg/kg, n=4), or an equivalent volume of vehicle (15% dimethyl sulfoxide, 15% cremophor EL, 70% saline, n=4) to manipulate the effect of endogenous adenosine on neuronal activities. Ten minutes after i.p. injection, rats are administered FDG (15.4±0.7 MBq) in 0.3-0.5 mL saline by intravenous (i.v.) tail vein injection. Rats are allowed to recover from anesthesia after the FDG injection but are reanesthetized for 15-minute-static PET scan with the head in the center of the field of view. All images are reconstructed[2].

IC50: 1.7 nM for adenosine kinase

Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation. Inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO, selectively increases ADO concentrations at sites of tissue trauma and enhances the analgesic and antiinflammatory actions of ADO. ABT 702 is a novel, potent nonnucleoside AK inhibitor.

In vitro: ABT 702 was active both in inhibiting AK (IC50 ) 1.7 nM) and ADO phosphorylation in the intact cells (IC50 ) 50 nM). ABT 702 was also highly selective for AK inhibition as compared to other sites of ADO action including ADA, ADO receptors, and ADO transport sites [1].

In vivo: ABT 702 had dose-dependent antinociceptive and antiinflammatory actions in a variety of animal models of nociceptive, inflammatory, and neuropathic pain. ABT 702 is the first of a novel class of potent, selective, non-nucleoside, orally active AK inhibitors that have potent antinociceptive effects in animal models [1].

Clinical trial: Up to now, ABT 702 is still in the preclinical development stage.

Reference:
[1] Lee CH, Jiang M, Cowart M, Gfesser G, Perner R, Kim KH, Gu YG, Williams M, Jarvis MF, Kowaluk EA, Stewart AO, Bhagwat SS.  Discovery of 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d]pyrimidine, an orally active, non-nucleoside adenosine kinase inhibitor.. J Med Chem. 2001 Jun 21;44(13):2133-8.