产品说明书
PF-06840003
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同义名 : | EOS200271 |
| CAS号 : | 198474-05-4 | |
| 货号 : | A196131 | |
| 分子式 : | C12H9FN2O2 | |
| 纯度 : | 99%+ | |
| 分子量 : | 232.21 | |
| MDL号 : | MFCD25121820 | |
| 存储条件： |
粉末 Inert atmosphere,Room Temperature 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 105 mg/mL(452.18 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
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| 动物实验配方： |
| 生物活性 | |||
|---|---|---|---|
| 描述 | IDO1 (Indoleamine 2,3-dioxygenase-1) is a heme-containing monomeric oxidoreductase, which can catalyze the degradation of the essential amino acid tryptophan to N-formyl-kynurenine, an intermediate metabolized through a series of steps to form NAD+. IDO1 is considered to play an important role in the induction of tumor immune tolerance, which can regulate the immunosuppressive mechanisms responsible for tumor escape from host immune surveillance. PF-06840003 is a selective IDO1 inhibitor with IC50 values of 0.41μM, 0.59μM and 1.5μM for hIDO-1, dIDO-1 and mIDO-1 (measured by enzymic acitivity), respectively. PF-06840003 is a racemic mixture, of which only the R-isomer is active, in development due to rapid epimerization of the chiral carbon that is adjacent to a carbonyl group. Incubation with PF-06840003 for 24h also showed significant inhibition on kynurenine production in HeLa, THP and human whole blood cells induced by INFγ or LPS[1], and reversed intratumoral KYN levels by >80% in vivo[2]. Oral administration of the PF-06840003 achieved total brain to plasma Kp ratio 0.51, indicating the brain penetrance of this compound[1]. Combination of PF-06840003 with immunotherapies including antibodies against PD-1 showed inhibition of tumor growth in multiple mouse syngeneic models[2]. | ||
| 作用机制 | PF-06840003 forms H-bond interaction with the propionate of the heme, not the heme iron atom, which is differently from most of the IDO-1 inhibitors described so far.[1] | ||
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
4.31mL 0.86mL 0.43mL |
21.53mL 4.31mL 2.15mL |
43.06mL 8.61mL 4.31mL |
