TG100-115

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的选择性 PI3Kγ/δ，IC50 分别为 83/235 nM；对 pI3Kα 和 β 以及多种激酶没有显着的抑制活性 (IC50>1 uM)。

A potent, selective PI3Kγ/δ with IC50 of 83/235 nM, respectively; shows no significant inhibitory activity against pI3Kα and β, and a broad panel of kinases (IC50>1 uM); potently inhibits edema and inflammation in response to multiple mediators known to participate in myocardial infarction, such as VEGF and platelet-activating factor, without effect on endothelial cell mitogenesis; provides potent cardioprotection, reduces infarct development and preserves myocardial function in animal MI models.COPD Discontinued(In Vitro):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 to participate in myocardial infarction, including vascular endothelial growth factor and platelet-activating factor; by contrast, endothelial cell mitogenesis, a repair process important to tissue survival after ischemic damage. (In Vivo):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.

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 to participate in myocardial infarction, including vascular endothelial growth factor and platelet-activating factor; by contrast, endothelial cell mitogenesis, a repair process important to tissue survival after ischemic damage.

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.

TG100115 | TG100 115

PI3K/Akt/mTOR signaling

PI3K

PI3Kα|PI3Kβ|PI3Kγ|PI3Kδ

Inflammation/Immunology

COPD

677297-51-7

346.3428

C18H14N6O2

>98% (HPLC)

10 mM in DMSO

OC1=CC=CC(C2=NC3=NC(N)=NC(N)=C3N=C2C4=CC=CC(O)=C4)=C1

Phenol, 3,3'-(2,4-diamino-6,7-pteridinediyl)bis-

(-20℃)

With Ice Pack

≥ 2 years