1648863-90-4

中文名称:

1648863-90-4

中文同义词:

PAK1抑制剂(G-5555)

英文名称:

G-5555

英文同义词:

G-5555;8-(((2r,5r)-5-Amino-1,3-dioxan-2-yl)methyl)-6-(2-chloro-4-(6-methylpyridin-2-yl)phenyl)-2-(met;G5555;G 5555;8-[(trans-5-Amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one;Pyrido[2,3-d]pyrimidin-7(8H)-one, 8-[(trans-5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(6-methyl-2-pyridinyl)phenyl]-2-(methylamino)-

CAS号:

1648863-90-4

分子式:

C25H25ClN6O3

分子量:

492.96

EINECS号:

相关类别:

细胞生物学试剂

Mol文件:

1648863-90-4.mol

沸点 

684.6±65.0 °C(Predicted)

密度 

1.363±0.06 g/cm3(Predicted)

酸度系数(pKa)

6.86±0.40(Predicted)

生物活性

G-5555 是有效 PAK1 抑制剂，对 PAK1 和 PAK2 的 Ki 值分别为 3.7 nM 和 11 nM。

靶点

PAK1 3.7 nM (Ki) PAK2 11 nM (Ki)

PAK1 3.7 nM (Ki)

PAK2 11 nM (Ki)

体外研究

G-5555 is a potent PAK1 inhibitor with a K i of 3.7 nM. G-5555 shows excellent kinase selectivity and inhibits only eight out of the 235 kinases tested other than PAK1 with inhibition >70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. The IC 50 s of G-5555 against SIK2, PAK2, KHS1, MST4, YSK1, MST3 and Lck are 9, 11, 10, 20, 34, 43, 52 nM, respectively. In general, G-5555 demonstrates high selectivity for the group I PAKs. There is negligible activity for G-5555 against the hERG channel with IC 50 more than 10 μM in a patch clamp assay. G-5555 potently inhibits PAK2, with a K i of 11 nM. In an array of 23 breast cancer cell lines, G-5555 has significantly greater growth inhibitory activity in cell lines that are PAK-amplified compared to non-amplified lines.

体内研究

G-5555 exhibits low blood clearance and an acceptable half-life. Good oral exposure (AUC = 30 μM•h) and high oral bioavailability (F = 80%) are achieved. In an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice, G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 and, when administered at an oral dose of 25 mg/kg b.i.d., imparts 60% tumor growth inhibition in this model13 and a PAK1 amplified breast cancer xenograft model, MDAMB-175.