BAY85-8501

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BAY 85-8501 (BAY85-8501) 是一种有效的、选择性的人中性粒细胞弹性蛋白酶 (HNE) 抑制剂，IC50 为 65 pM。

BAY 85-8501 (BAY85-8501) is a potent, selective human neutrophil elastase (HNE) inhibitor with IC50 of 65 pM; displays no significant inhibition toward 21 related serine proteases (>30 uM); demonstrates completely prevented the development of lung injury and subsequent inflammation in vivo.COPD Phase 2 Clinical.

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In this model the exogenous HNE noxa is the primary cause of injury and lung hemorrhage. Based on picomolar potency against HNE as well as single digit potency versus MNE, BAY-85-8501 (29) completely prevents the development of lung injury and subsequent inflammation when administered 1 h prior to the HNE noxa. In the 0.01 mg/kg dose group, hemoglobin concentration is already significantly decreased. At a dose of 0.1 mg/kg, a significant effect on neutrophil count is observed. In this setup, efficacy is predominantly driven by potency against HNE (Ki=0.08 nM). As the highly HNE-selective inhibitor BAY 85-8501 has no effect on PPE, BAY-85-8501 could not prevent the primary lung injury in this setup. Nevertheless, BAY-85-8501 could inhibit MNE, the endogenous driver of inflammation and secondary injury, although with decreased potency. Consequently, the effects of BAY-85-8501 on inflammation and secondary injury are weaker at this point, and only observed at 30-fold higher doses. Efficacy is predominantly driven by potency against MNE (Ki=6 nM) in this second setup.

BAY 85-8501 | BAY 858501

Metabolic Enzyme/Protease

Elastase

Elastase

Inflammation/Immunology

COPD

1161921-82-9

474.458

C22H17F3N4O3S

>98% (HPLC)

In Vitro:?DMSO : 200 mg/mL (421.53 mM)

N#CC1=C(C)N(C2=CC=CC(C(F)(F)F)=C2)C(N(C)[C@@H]1C3=CC=C(C#N)C=C3S(=O)(C)=O)=O

(S)-4-(4-cyano-2-(methylsulfonyl)phenyl)-3,6-dimethyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine-5-carbonitrile

(-20℃)

With Ice Pack

≥ 2 years