4-氨基-1-环戊基-3-(4-苯氧基苯基)-1H-吡唑并[3,4-D]嘧啶

中文名称:

4-氨基-1-环戊基-3-(4-苯氧基苯基)-1H-吡唑并[3,4-D]嘧啶

中文同义词:

4-氨基-1-环戊基-3-(4-苯氧基苯基)-1H-吡唑并[3,4-D]嘧啶;化合物PCI29732

英文名称:

PCI 29732

英文同义词:

PCI 29732;4-Amino-1-cyclopentyl-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidine;1-Cyclopentyl-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;PCI 29732 (This product is only available in Japan.);CS-2698;PCI 29732;PCI29732;PCI-29732;1H-Pyrazolo[3,4-d]pyrimidin-4-amine, 1-cyclopentyl-3-(4-phenoxyphenyl)-

CAS号:

330786-25-9

分子式:

C22H21N5O

分子量:

371.43

EINECS号:

相关类别:

Mol文件:

330786-25-9.mol

沸点 

599.6±50.0 °C(Predicted)

密度 

1.36±0.1 g/cm3(Predicted)

酸度系数(pKa)

4.24±0.30(Predicted)

CAS 数据库

330786-25-9

生物活性

PCI 29732是一种选择性的、不可逆的Btk抑制剂，IC50为0.5 nM。

靶点

Target Value BTK (Cell-free assay) 0.5 nM BLK (Cell-free assay) 0.5 nM Bmx (Cell-free assay) 0.8 nM EGFR (Cell-free assay) 5.6 nM YES (Cell-free assay) 6.5 nM

Target

Value

BTK (Cell-free assay)

0.5 nM

BLK (Cell-free assay)

0.5 nM

Bmx (Cell-free assay)

0.8 nM

EGFR (Cell-free assay)

5.6 nM

YES (Cell-free assay)

6.5 nM

体外研究

PCI29732 shows cytotoxicity in different cells. The IC 50 values are 7.94 μM for S1, 7.79 μM for S1-MI-80, 6.55 μM for H460, 6.34 μM for H460/MX20, 6.14 μM for KB, 6.02 μM for KBv200, 12.45 μM for HEK293/pcDNA3, 14.58 μM for HEK293-ABCG2-482-R2, and 13.24 μM for HEK293-ABCG2-482-T7 cells. PCI-29732 blocks the transcriptional up-regulation of a panel of B-cell activation genes in human CD20+ B cells stimulated at the B-cell antigen receptor (BCR).

体内研究

PCI 29732 inhibits the function of ABCG2 by competitively binding to the ATP-binding site of ABCG2 and enhances the anti-tumor efficacy of substrate chemotherapeutic agents. PCI 29732 (20 mg/kg; p.o.; every 3 d × 5 times) enhances the anticancer efficacy of Topotecan in the H460/MX20 cell xenograft nude mice model. Animal Model: 5-6 weeks old athymic nude mice (bearing H460/MX20 cells) Dosage: 20 mg/kg (combination with Topotecan; every 3 d × 5 times, i.p., 3 mg/kg; topotecan was given 1 h after PCI29732 administration) Administration: P.o.; every 3 d × 5 times Result: Significant reductions in tumor weight and volume were observed in the group treated with PCI29732 in combination with Topotecan.

Animal Model:

5-6 weeks old athymic nude mice (bearing H460/MX20 cells)

Dosage:

20 mg/kg (combination with Topotecan; every 3 d × 5 times, i.p., 3 mg/kg; topotecan was given 1 h after PCI29732 administration)

Administration:

P.o.; every 3 d × 5 times

Result:

Significant reductions in tumor weight and volume were observed in the group treated with PCI29732 in combination with Topotecan.