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.
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- CAS No.: 144928-48-3
- Formule: C10H13BrN6O3
- Masse moléculaire:345.15
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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.
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Cell Line:cultured rat myocardial myoblasts (RMMs)
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Concentration:0.2 μM; 2 μM; 20 μM; 200 μM
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Incubation Time:18 h
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Result:Increased VEGF protein levels to 1.99 ng/mg total cell protein (8% increase) at 0.2 μM.
Increased VEGF protein levels to 2.50 ng/mg total cell protein (36% increase) at 2 μM.
Increased VEGF protein levels to 2.56 ng/mg total cell protein (39% increase) at 20 μM.
Increased VEGF protein levels to 2.84 ng/mg total cell protein (54% increase) at 200 μM; control VEGF protein levels were 1.84 ng/mg total cell protein, with all increases statistically significant.
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Cell Line:cultured rat myocardial myoblasts (RMMs)
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Concentration:1 μM
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Incubation Time:2 h; 6 h; 12 h; 24 h
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Result:Did not significantly increase VEGF protein levels after 2 or 6 h of incubation.
Caused a significant 20% increase after 12 h.
Continued to increase levels such that by 24 h, levels were quantitatively similar to those induced by equimolar adenosine.
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Cell Line:cultured rat myocardial myoblasts (RMMs)
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Concentration:2 μM (co-incubated with 10 U/mL adenosine deaminase)
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Incubation Time:18 h
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Result:Co-incubation with adenosine deaminase completely blocked the GP515-induced increase in VEGF protein, reducing levels to 0.75 ng/mg total cell protein, a 60% decrease compared to control levels of 1.84 ng/mg total cell protein.
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Cell Line:human umbilical vein endothelial cells (HUVECs), rat myocardial myoblasts (RMMs)
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Concentration:20 μM
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Incubation Time:24 h
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Result:Increased HUVEC cell number by 98% (from control 8.5 × 105 cells/well).
Increased [3H]thymidine incorporation by 82% (from control 11.91 × 103 cpm/well), with both changes statistically significant.
Had no effect on RMM proliferation.
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Cell Line:cultured rat myocardial myoblasts (RMMs)
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Concentration:20 μM
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Incubation Time:18 h (under normoxia, mild hypoxia, severe hypoxia)
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Result:Increased VEGF protein levels by 37% (to 2.79 ng/mg total cell protein) compared to normoxic control levels of 2.04 ng/mg total cell protein under normoxia.
Increased VEGF protein levels by an additional 27% (to 4.17 ng/mg total cell protein) compared to mild hypoxia control levels of 3.29 ng/mg total cell protein under mild hypoxia.
Had no effect on VEGF protein levels (5.84 ng/mg total cell protein vs.
severe hypoxia control levels of 6.06 ng/mg total cell protein) under severe hypoxia.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (female, 200-250 g, pressure-controlled hemorrhagic hypotension induced by blood withdrawal to maintain mean arterial pressure at 40 mmHg for 90 minutes, followed by resuscitation with 60% shed blood and lactate Ringer’s solution)[1]
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Dosage:0.25 mg/kg
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Administration:i.v.; continuous infusion over 1 hour; starting 90 minutes after onset of hemorrhagic hypotension
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Result:Increased sinusoidal blood flow to 40833 µm3/s, mean sinusoidal diameter to 12.08 µm, and perfusion index to 91.5% at 2 days post-shock, with all values significantly higher than placebo.
Normalized sinusoidal diameters, blood flow, and perfusion index by 5 days post-shock, with no significant difference from placebo-treated rats.
Chemical Information
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CAS No. 144928-48-3
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Masse moléculaire 345.15
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Formule C10H13BrN6O3
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SMILES
O[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(N)=C3C(Br)=N2)O[C@@H]1CN
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[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. [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GP515 Related Classifications
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