TG100-115 is a selective PI3Kγ/PI3Kδ inhibitor with IC₅₀s of 83 and 235 nM, respectively.

TG100-115 inhibits PI3Kγ and PI3Kδ with IC₅₀s of 83 and 235 nM, respectively, whereas both PI3Kα and PI3Kβ are relatively unaffected (IC₅₀ values >1 μM). As a gauge of general specificity, TG100-115 is also assayed against a 133 protein kinase panel, none of which are inhibited at IC₅₀ values <1 μm. tg100-115 potently inhibits edema and inflammation in response to multiple mediators known participate myocardial infarction, including vascular endothelial growth factor platelet-activating factor; by contrast, cell mitogenesis, a repair process important tissue survival after ischemic damage^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

To correlate these in vivo responses with the molecular target of interest, PI3K pathway signaling is monitored through western blot analyses of Akt phosphorylation (a PI3K-mediated event). VEGF injection i.v. in mice induces a rapid Akt phosphorylation readily detectable in lung lysates, pretreatment with TG100-115 blocks this response. Blockade is seen with TG100-115 doses as low as 0.5 mg/kg and persists over a period of several hours. In initial dose-ranging studies, generally equivalent responses are observed using TG100-115 doses of 0.5-10 mg/kg, and we therefore elected to conduct a statistically powered test at the lowest dose. Animals dosed with TG100-115 as a single 0.5 mg/kg i.v. bolus 30 min after reperfusion developed smaller infarcts vs. vehicle-treated controls. Measuring infarct area as percent of total LV ischemic area, infarct size is reduced by 35% (P=0.04). Viable tissue within the ischemic zone is increased by 37% (P=0.04), directly demonstrating the cardioprotective effect of PI3Kγ/δ inhibition^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

346.34

C₁₈H₁₄N₆O₂

677297-51-7

Room temperature in continental US; may vary elsewhere.

DMSO : 5.45 mg/mL (15.74 mM; Need ultrasonic and warming)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

• [1]. Doukas J, et al. Phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19866-71.

PI3K reactions are constructed by using recombinant human kinases, 3 μM ATP, phosphatidylinositol substrate, and cofactors, and reaction progression measured by using a luminescent-based detection system to quantify ATP consumption. Protein kinase assays are performed by using commercial screening services^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Human umbilical vein EC plated in 96-well cluster plates (5,000 cells/well) are cultured in assay medium (containing 0.5% serum and 50 ng/mL VEGF) in the presence or absence of test compounds (e.g., TG100-115) (10 μM), and cell numbers are quantified by XTT assay 24, 48, or 72 h later^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Rats^[1]
Sprague-Dawley rats (175-200 g) are dosed i.v. with either TG100-115 (1 mg/kg) or vehicle, and 1-4 h later Evans blue dye is administered i.v. as 500 μl of a 2% sterile saline solution. Immediately after dye injection, animals are injected intradermally on each shaved flank with 100 μL of saline, VEGF (2 μg/mL stock), or histamine (10 μg/mL stock). Thirty minutes later, injection sites are photographed.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Doukas J, et al. Phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19866-71.