BF738735

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

BF738735 是一种新型广谱肠道病毒复制抑制剂 (EC50=4-71 nM)，专门针对宿主细胞因子 PI4KIIIβ，IC50 为 5.7 nM。

BF738735 is a novel, broad-spectrum inhibitor of enterovirus replication (EC50=4-71 nM) that specifically targets host cell factor PI4KIIIβ with IC50 of 5.7 nM, 300-fold less potent for PI4KIIIα (IC50=1.7 uM); blocks viral RNA replication with IC50 of 77 nM in luciferase assays, strongly inhibits CVB3 and EV71 replicon replication at 1-5 uM; reduces the PI4P levels at the Golgi complex through a direct inhibition of PI4KIIIβ activity.

BF738735 (Compound 1) strongly inhibits PI4KIIIβ activity in vitro, with an IC50 of 5.7 nM. BF738735 also impairs PI4KIIIα, but only at an ~300-fold-higher concentration (IC50 of 1.7 μM). In addition, the activity of BF738735 is analyzed on a set of 150 cellular kinases, including 13 lipid kinases at a concentration of 10 μM. For all kinases, the inhibition is less than 10%, indicating that BF738735 specifically inhibits PI4KIIIβ in vitro. BF738735 exhibits a broad spectrum of antiviral activity, as it inhibits all tested species of enteroviruses and rhinoviruses, with 50% effective concentrations ranging between 4 and 71 nM. BF738735 potently inhibits all viruses tested, with EC50s ranging between 4 and 71 nM. The cytotoxicity of BF738735, determined in parallel with the EC50 and using the same culture conditions for 3 to 4 days, is low, with CC50 values ranging from 11 to 65 μM, resulting in high selectivity indices. Low concentrations of BF738735 reduce the amount of luciferase to GuaHCl-treated levels, suggesting that the BF738735 blocks viral RNA replication. The EC50 of BF738735 in this assay is 77 nM, which is comparable to the inhibition observed in the multicycle assay for coxsackievirus serotype B3 (CVB3).

BF738735 is well tolerated by specimens with good plasma levels of the antiviral in circulation and a complete inhibition with 25 mg/kg and some inhibition with 5 mg/kg dose is observed.

BF 738735 | BF-738735

Microbiology/Virology

Enterovirus

Enterovirus

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1436383-95-7

426.466

C21H19FN4O3S

>98% (HPLC)

DMSO : 125 mg/mL 293.11 mM

OC1=CC=C(C=C1F)C2=C(C)N=C3C(NCC4=CC=CC(S(=O)(C)=O)=C4)=NC=CN32

2-fluoro-4-(2-methyl-8-((3-(methylsulfonyl)benzyl)amino)imidazo[1,2-a]pyrazin-3-yl)phenol

(-20℃)

With Ice Pack

≥ 2 years