1445879-21-9

中文名称:

1445879-21-9

中文同义词:

乳酸脱氢酶A(LDHA)抑制剂(GSK2837808A);化合物GSK2837808A

英文名称:

GSK2837808A

英文同义词:

GSK2837808A;GSK 2837808A (GSK2837808A);3-[[3-[(Cyclopropylamino)sulfonyl]-7-(2,4-dimethoxy-5-pyrimidinyl)-4-quinolinyl]amino]-5-(3,5-difluorophenoxy)benzoic acid;Benzoic acid, 3-[[3-[(cyclopropylamino)sulfonyl]-7-(2,4-dimethoxy-5-pyrimidinyl)-4-quinolinyl]amino]-5-(3,5-difluorophenoxy)-

CAS号:

1445879-21-9

分子式:

C31H25F2N5O7S

分子量:

649.62

EINECS号:

相关类别:

细胞生物学试剂

Mol文件:

1445879-21-9.mol

沸点 

783.5±70.0 °C(Predicted)

密度 

1.57±0.1 g/cm3(Predicted)

酸度系数(pKa)

3.81±0.10(Predicted)

生物活性

GSK 2837808A 是一种选择性的 LDHA (lactate dehydrogenase A) 的抑制剂，对hLDHA和hLDHB的IC50分别为2.6 nM和43 nM。

靶点

Target Value hLDHA (Cell-free assay) 2.6 nM hLDHB (Cell-free assay) 43 nM

Target

Value

hLDHA (Cell-free assay)

2.6 nM

hLDHB (Cell-free assay)

43 nM

体外研究

GSK2837808A rapidly and profoundly inhibits lactate production rates in multiple cancer cell lines including hepatocellular and breast carcinomas. The potency of GSK2837808A across 30 cancer cell lines with different LDHA and LDHB expression levels ranges from 400 nM to no effect (EC 50 reported as 30 μM). GSK2837808A potency does not correlate with LDHA, LDHB, or the total LDH expression levels. GSK2837808A inhibits lactate production in hypoxia but at higher concentrations than in normoxia (EC 50 =10 μM). It also reduces ECAR with EC 50 =10 μM. LDH inhibition by GSK2837808A alters multiple metabolic pathways in Snu398 cells.

体内研究

Clearance following IV infusion of GSK2837808A at 0.25 mg/kg is shown to be 69 mL/minute/kg in rats, which exceeds the animal liver blood flow. Oral dosing of GSK2837808A at 50 mg/kg in rats or 100 mg/kg in mice results in blood compound levels at or below the detection limit of 2.5 ng/mL.