GP515 

GP515 is a potent and selective adenosine kinase inhibitor with a human IC₅₀ of 4 nM. GP515 exerts tissue protective effects, produces long-lasting hepatic microcirculation effects after hemorrhagic shock, and induces dose- and time-related VEGF mRNA and protein expression in normoxic rat myocardial myoblasts, with additive VEGF increases during mild hypoxia and no effect during severe hypoxia. GP515 suppresses IFNγ synthesis and CD69 expression in DSS-induced colitis. GP515 also shows a dose-dependent suppression of TNF-α production with an IC₅₀ of 80 μM and can be reversed in the presence of the cAMP antagonist (Rp)-cAMPS. Combinations of GP515 with either adenosine or rolipram led to an additive inhibition of TNF-α synthesis. GP515 can be used for the research of hemorrhagic shock^[1][2][3][4].

GP515 potently and specifically inhibits isolated human cardiac adenosine kinase with an IC₅₀ of 4 nM^[2].
GP515 (2-20 μM; 18 h) increases VEGF mRNA expression in cultured rat myocardial myoblasts by 1.67-fold and 1.82-fold, respectively, after 18 h of normoxic incubation^[2].
GP515 (0.2-200 μM; 18 h) induces a dose-related increase in VEGF protein expression in cultured rat myocardial myoblasts after 18 h of normoxic incubation, reaching up to a 54% increase at the highest concentration^[2].
GP515 (1 μM; 12-24 h) significantly increases VEGF protein expression in cultured rat myocardial myoblasts after 12 h of normoxic incubation, with effects persisting through 24 h^[2].
GP515 (2 μM; 18 h) co-incubated with adenosine deaminase completely blocks the VEGF protein-inducing effect in cultured rat myocardial myoblasts after 18 h of normoxic incubation^[2].
GP515 (20 μM; 24 h) stimulates human umbilical vein endothelial cell proliferation by 98% and increases [³H]thymidine incorporation by 82% after 24 h of incubation, with no effect on rat myocardial myoblast proliferation^[2].
GP515 (20 μM; 18 h) increases VEGF protein expression in cultured rat myocardial myoblasts by 37% under normoxia and by an additional 27% under mild hypoxia (10% O₂) after 18 h of incubation, but has no effect under severe hypoxia (1% O₂)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Systemic administration of GP515 (0.25 mg/kg; i.v.; continuous infusion over 1 hour; starting 90 minutes after onset of hemorrhagic hypotension) after hemorrhagic shock significantly improves hepatic microcirculatory parameters (sinusoidal blood flow, diameter, and perfusion index) at 2 days post-shock, with normalization of these parameters by 5 days in female Sprague-Dawley rats (200–250 g)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

345.15

C₁₀H₁₃BrN₆O₃

144928-48-3

O[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(N)=C3C(Br)=N2)O[C@@H]1CN

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Bulut K, et al. Long-Term Effects of the Adenosine Kinase Inhibitor GP-515 on Hepatic Microcirculation Following Hemorrhagic Shock. Eur J Trauma. 2003;29:139–144.

  [2]. Gu JW, et al. Inhibition of adenosine kinase induces expression of VEGF mRNA and protein in myocardial myoblasts. Am J Physiol Heart Circ Physiol. 2000;279(5):H2116-H2123.

  [3]. Siegmund B, Rieder F, Albrich S, Wolf K, Bidlingmaier C, Firestein GS, Boyle D, Lehr HA, Loher F, Hartmann G, Endres S, Eigler A. Adenosine kinase inhibitor GP515 improves experimental colitis in mice. J Pharmacol Exp Ther. 2001 Jan;296(1):99-105.

  [4]. Eigler A, Matschke V, Hartmann G, Erhardt S, Boyle D, Firestein GS, Endres S. Suppression of TNF-alpha production in human mononuclear cells by an adenosine kinase inhibitor. J Leukoc Biol. 2000 Jul;68(1):97-103.