Pico145, also known as HC-608, is a notable inhibitor of TRPC1/4/5 channels, suppressing (−)-englerin A-activated TRPC4/TRPC5 channels with IC50 values of 0.349 nM and 1.3 nM in cells, respectively, without affecting the cells. Pico145 also inhibits human TRPC4-TRPC1 and TRPC5-TRPC1 heteromers expressed in HEK 293 Tet+ cells, with IC50 values of 0.03 nM and 0.2 nM, respectively. The potency of Pico145 can be diminished by increasing concentrations of (−)-englerin A. Moreover, Pico145 effectively inhibits 1-phosphatidylsphingosine (S1P) activated TRPC4-TRPC1 channels and suppresses S1P-induced Ca2+ entry through TRPC4-TRPC1 channels, with an IC50 of 0.011 nM. Pico145 also sensitizes EA-sensitive cancer cell lines (Hs578T cells) with an IC50 of 0.11 nM. At 100 nM, Pico145 does not affect store-operated Ca2+ entry into endothelial cells or histamine-induced Ca2+ entry into endothelial cells[1].
Pico145 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Cortical neurons
200 nM
15 min
Blocks the NCAM antibody-triggered increase in Fluo-4 AM signal intensity
Int J Mol Sci. 2022 Sep 2;23(17):10027
Mouse CA1 pyramidal cells
100 nM
15-30 minutes
To test the inhibitory effect of Pico145 on cholinergically induced persistent firing. In five out of six cells, persistent firing was completely blocked, and in the remaining cell, persistent firing was strongly reduced.
Cells. 2020 Feb 5;9(2):365
Hippocampal neurons
1 nM
40 minutes
Inhibition of TRPC1/4/5 channels, mimicking the effects of TRPC1 genetic depletion on synaptic plasticity.
Front Cell Neurosci. 2018 Sep 14;12:318
Pico145 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Morris Water Maze test
Intraperitoneal injection
0.1 mg/kg
Injected one hour before each probe test, for 5 days
To evaluate the effect of Pico145 on spatial memory extinction, results showed that Pico145 significantly impaired memory extinction.
Int J Mol Sci. 2020 Mar 3;21(5):1712
Mice
Trpc1 knockout mice
Brain slice perfusion
1 nM
Single administration, lasting 40 minutes
To investigate the role of TRPC1 in synaptic plasticity and spatial working memory. Pico145 inhibited TRPC1/4/5 channels, mimicking the effects of TRPC1 genetic depletion on LTP and LTD.
Front Cell Neurosci. 2018 Sep 14;12:318
Mice
Wild-type and NCAM-deficient mice
In vitro culture
200 nM
Single treatment, 15 min
Reduces the NCAM-stimulated Ca2+ response and neurite outgrowth
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