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GSK2292767
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GSK2292767图片
CAS NO:1254036-66-2
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件

Molecular Weight (MW)

512.58

Formula

C24H28N6O5S

CAS No.

1254036-66-2

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 100 mg/mL (195.1 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

SMILES

CS(=O)(NC1=CC(C2=CC3=C(C(C4=NC=C(CN5C[C@@H](C)O[C@@H](C)C5)O4)=C2)C=NN3)=CN=C1OC)=O

Synonyms

GSK2292767; GSK-2292767; GSK 2292767

实验参考方法

In Vitro

In vitro activity: GSK2292767 was found to be greater than 100-fold selective against a panel of in-house kinases and in the Millipore panel. Moreover, GSK2292767 could inhibit both IFNγ and IL-2 production in a concentration-dependent manner in a human lung parenchyma assay, with pIC50s of 8.7 and 8.5, respectively.

Kinase Assay: Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.

In Vivo

In a rat PK study, the in vivo clearance for GSK2292767 was significantly higher than that for its analog GSK2269557. The oral bioavailability was also low (F < 2%), which was consistent with the data observed for GSK2269557. In a rabbit cardiac ventricular wedge assay, no effect on QT interval, Tpe, or QRS and no significant risk of TdP arrhythmias was observed for GSK2292767 over the concentration range tested, thus indicating GSK2292767 could successfully mitigate the risk associated with GSK2269557. Moreover, GSK2292767 was found to protect against eosinophil recruitment with an ED50 of 35 μg/kg in the brown Norway rat acute OVA model, which was similar to GSK2269557.

Animal model

Rats

Formulation & Dosage


References

J Med Chem. 2015 Sep 24;58(18):7381-99.