Pico145 (HC-608) is a remarkable inhibitor of TRPC1/4/5 channels, inhibits (−)-englerin A-activated TRPC4/TRPC5 channels, with IC₅₀s of 0.349 and 1.3 nM in cells, and shows no effect on TRPC3, TRPC6, TRPV1, TRPV4, TRPA1, TRPM2, TRPM8^[1].

IC50: 0.349 nM (TRPC4, cell assay), 1.3 nM (TRPC5, cell assay), 0.03 nM (TRPC4-TRPC1, cell assay), 0.2 nM (TRPC5-TRPC1, cell assay)^[1]

Pico145 (Compound 31, C31) is a remarkable small-molecule inhibitor of TRPC1/4/5 channels, inhibits (−)-englerin A-activated TRPC4/TRPC5 channels, with IC₅₀s of 0.349 and 1.3 nM in cells; Pico145 shows no effect on TRPC3, TRPC6, TRPV1, TRPV4, TRPA1, TRPM2, TRPM8. Pico145 also inhibits human TRPC4-TRPC1 and TRPC5-TRPC1 concatemers expressed in HEK 293 Tet⁺ cells (IC₅₀, 0.03 nM and 0.2 nM, respectively). The potency of Pico145 can be reduced by increased (−)-englerin A concentration. Furthermore, Pico145 potently inhibits RPC4-TRPC1 channels activated by sphingosine 1-phosphate (S1P), and suppresses S1P-evoked Ca²⁺ entry through TRPC4-TRPC1 channels with an IC₅₀ of 0.011 nM. Pico145 also sensitizes EA-sensitive cancer cell line (Hs578T cells) (IC₅₀, 0.11 nM). Pico145 (100 nM) lacks effect on store-operated Ca²⁺ entry and histamine-evoked Ca²⁺ entry into endothelial cells^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

524.88

C₂₃H₂₀ClF₃N₄O₅

1628287-16-0

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL (190.52 mM)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (4.76 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.76 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (4.76 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.76 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Rubaiy HN, et al. Picomolar, selective, and subtype-specific small-molecule inhibition of TRPC1/4/5 channels. J Biol Chem. 2017 May 19;292(20):8158-8173.

Cells are seeded at 90% confluence into 96-well clear-bottomed poly-d-lysine-coated black plates for HEK 293 cells and clear-bottomed Nunc plates for A498 cells, Hs578T cells, and HUVECs 24 h before experimentation. Fura-2 Ca²⁺ indicator dye is used to monitor changes in intracellular ionized Ca²⁺ concentration. To perform the experiment, the cells are incubated for 1 h with fura-2-AM (2 μM) in standard bath solution (SBS) at 37°C in the presence of 0.01% pluronic acid. SBS contains 135 mM NaCl, 5 mM KCl, 1.2 mM MgCl₂, 1.5 mM CaCl₂, 8 mM glucose, and 10 mM Hepes (pH titrated to 7.4 using NaOH). Subsequently, the cells are washed twice with SBS before adding Pico145 or ML204 for 30 min before making Ca²⁺ measurements. The fura-2 fluorescence is recorded using a 96-well fluorescence plate reader and the excitation wavelengths of 340 and 380 nm^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Rubaiy HN, et al. Picomolar, selective, and subtype-specific small-molecule inhibition of TRPC1/4/5 channels. J Biol Chem. 2017 May 19;292(20):8158-8173.