Pyr10

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

Pyr10 是一种吡唑衍生物，也是一种选择性 TRP 阳离子 3 抑制剂。 Pyr10 能够区分受体操作的 TRPC3 和天然基质相互作用分子 1 (STIM1)/Orai1 通道。 Pyr10 抑制卡巴胆碱刺激的 TRPC3 转染 HEK293 细胞中的 Ca2+ 流入（IC50：0.72 μM）（BRL-2H3 细胞中钙池操纵的 Ca2+ 进入的 IC50 为 13.08 μM）。

Pyr10 is a pyrazole derivative and a selective TRP cation 3 inhibitor. Pyr10 has the ability to distinguish between receptor-operated TRPC3 and native stromal interaction molecule 1 (STIM1)/Orai1 channels. Pyr10 inhibits Ca2+ influx in carbachol-stimulated TRPC3-transfected HEK293 cells (IC50: 0.72 μM) (IC50 of 13.08 μM for store-operated Ca2+ entry in BRL-2H3 cells) . The novel pyrazole Pyr10 displayed substantial selectivity for TRPC3-mediated responses (18-fold) and the selective block of TRPC3 channels by Pyr10 barely affected mast cell activation.Pyr10 blunted ventricular CF activation and MF in l-NAME hypertensive mice.?Finally, TRPC3 was present in human ventricular CFs and upregulated in MF, whereas pharmacological modulation of TRPC3-NFATc3 decreased proliferation and collagen secretion.?TRPC3-NFATc3 signaling is modulated by P.E. and critically regulates ventricular CF phenotype and MF.?These findings strongly argue for P.E., through TRPC3 targeting, as potential and interesting therapeutics for MF management.

Pyr10 has the ability to discriminate between the classical Orai-mediated, highly Ca2+ selective signalling pathway and the phospholipase C-dependent Ca2+ entry-mediated by TRPC channels, specifically by TRPC3. Pyr10 (3 μM) completely eliminates TRPC3 currents as well as Ca2+ entry while exerting modest effects on Orai-mediated responses. The selective block of TRPC3 channels by Pyr10 barely affected mast cell activation.

Genetic deletion (TRPC3-/-) and pharmacological channel blockade with Pyr10 blunts ventricular cardiac fibroblast activation and myocardial fibrosis in N(ω)-nitro-l-arginine methyl ester (l-NAME) hypertensive mice.

——

Membrane Transporter/Ion Channel

TRP/TRPV Channel

TRPC3

——

——

1315323-00-2

449.37

C18H13F6N3O2S

>98% (HPLC)

DMSO:95 mg/mL (211.4 mM; Need ultrasonic)

Cc1ccc(cc1)S(=O)(=O)Nc1ccc(cc1)-n1nc(cc1C(F)(F)F)C(F)(F)F

——

(-20℃)

With Ice Pack

≥ 2 years