Pico145 (HC-608)是一种TRPC1/4/5通道抑制剂，可抑制(-)-englerin A激活的TRPC4/TRPC5通道，IC50值分别为0.349nM和1.3nM。
Cas No.:1628287-16-0
Sample solution is provided at 25 µL, 10mM.
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Pico145 (HC-608) is a TRPC1/4/5 channel inhibitor, which can inhibit the TRPC4/TRPC5 channels activated by (-)-englerin A with the IC50 values of 0.349 and 1.3nM, respectively [1]. Pico145 can bind to up to four lipid binding sites between the TRPC5 subunits and replace the phospholipids that interact with the channel pore helices [2]. Pico145 has been widely used to inhibit intracellular Ca2+ influx in cells and to screen agonists of TRPC1/4/5 channels[3].
In vitro, Pico145 treatment (10nM) for 48 hours significantly inhibited (-)-englerin A-induced cell death in SW982 cells and restored cell viability[4]. Treatment with 100nM Pico145 for 15 minutes blocked the sustained firing of CA1 pyramidal cells[5].
In vivo, Pico145 treatment via daily intraperitoneal injection at a dose of 0.1mg/kg for 5 days led to the impairment of spatial memory extinction in Trpc1−/− mice[6].
References:
[1] Rubaiy H N, Ludlow M J, Henrot M, et al. Picomolar, selective, and subtype-specific small-molecule inhibition of TRPC1/4/5 channels[J]. Journal of Biological Chemistry, 2017, 292(20): 8158-8173.
[2] Wright D J, Simmons K J, Johnson R M, et al. Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site[J]. Communications Biology, 2020, 3(1): 704.
[3] Rubaiy H N, Ludlow M J, Siems K, et al. Tonantzitlolone is a nanomolar potency activator of transient receptor potential canonical 1/4/5 channels[J]. British Journal of Pharmacology, 2018, 175(16): 3361-3368.
[4] Muraki K, Ohnishi K, Takezawa A, et al. Na+ entry through heteromeric TRPC4/C1 channels mediates (−) Englerin A-induced cytotoxicity in synovial sarcoma cells[J]. Scientific reports, 2017, 7(1): 16988.
[5] Arboit A, Reboreda A, Yoshida M. Involvement of TRPC4 and 5 channels in persistent firing in hippocampal CA1 pyramidal cells[J]. Cells, 2020, 9(2): 365.
[6] Yerna X, Schakman O, Ratbi I, et al. Role of the TRPC1 channel in hippocampal long-term depression and in spatial memory extinction[J]. International journal of molecular sciences, 2020, 21(5): 1712.
Pico145 (HC-608)是一种TRPC1/4/5通道抑制剂，可抑制(-)-englerin A激活的TRPC4/TRPC5通道，IC50值分别为0.349nM和1.3nM[1]。Pico145可与TRPC5亚基之间多达四个脂质结合位点结合，并取代与通道孔螺旋相互作用的磷脂[2]。Pico145已被广泛用于抑制细胞内的Ca2+内流以及筛选TRPC1/4/5通道的激动剂[3]。
在体外，使用10nM的Pico145处理SW982细胞48小时，显著抑制了(-)-englerin A诱导的细胞死亡并恢复了细胞活力[4]。使用100nM的Pico145处理15分钟，阻断了CA1锥体细胞的持续放电[5]。
在体内，每日腹腔注射0.1mg/kg剂量的Pico145，连续5天，导致Trpc1−/−小鼠的空间记忆消退受损[6]。
| Cell experiment [1]: | |
Cell lines | SW982 cells |
Preparation Method | SW982 cells were cultured in L-15 medium supplemented with 10% heat-inactivated fetal calf serum (FCS), 100U/ml penicillin, 100mg/ml streptomycin in 5% CO2 at 37°C. Cells were placed in a 96 well-plate at a concentration of 1×104 cells per well and were treated with Pico145 (10nM) and 30nM (-)-englerin A for 48h, and then the cell viability was analyzed. |
Reaction Conditions | 10nM; 48h |
Applications | Pico145 significantly inhibited (-)-englerin A-induced cell death in SW982 cells and restored cell viability. |
| Animal experiment [2]: | |
Animal models | Trpc1−/− mice |
Preparation Method | Male Trpc1−/− mice (3-month-old) were housed in a specialized animal care facility, in a room with constant temperature (25°C), humidity control, and a 12/12h light/dark cycle with free access to food and water. The Morris Water Maze (MWM) was used to assess spatial learning and memory. The water maze was made of a round pool with a diameter of 113cm virtually divided into four quadrants (North, South, West, and East) and was filled with water (26°C). Several visual cues were placed around the pool and a platform was placed at the center of the North-East quadrant of the pool. Mice were trained in a water maze from day 1 to day 5. Memory extinction was studied by repeated probe tests from day 8 to day 12. During this period, one hour before each probe test, the mice were injected intraperitoneally with 0.1mg/kg weight Pico145 or with vehicle. |
Dosage form | 0.1mg/kg/day for 5 days; i.p. |
Applications | Pico145 treatment significantly impaired spatial memory extinction in Trpc1−/− mice. |
References: | |
| Cas No. | 1628287-16-0 | SDF | |
| 别名 | HC-608 | ||
| Canonical SMILES | O=C1C2=C(N=C(OC3=CC=CC(OC(F)(F)F)=C3)N2CC4=CC=C(Cl)C=C4)N(C)C(N1CCCO)=O | ||
| 分子式 | C23H20ClF3N4O5 | 分子量 | 524.88 |
| 溶解度 | DMSO : ≥ 125 mg/mL (238.15 mM) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9052 mL | 9.526 mL | 19.052 mL |
| 5 mM | 381 μL | 1.9052 mL | 3.8104 mL |
| 10 mM | 190.5 μL | 952.6 μL | 1.9052 mL |
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| % DMSO % % Tween 80 % saline | ||||||||||
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