T16Ainh-A01, an aminophenylthiazole, is a potent transmembrane protein 16A (TMEM16A) inhibitor, inhibiting TMEM16A-mediated chloride currents with an IC50 value of ~1 µM. TMEM16A (ANO1) functions as a calcium-activated chloride channel (CaCC). Depolarization-evoked I ClCa in isolated RUICC, recorded using voltage clamp, were inhibited by T16Ainh-A01 with IC50 values of 3.4 μM. Eurogenic contractions of strips of rabbit urethra smooth muscle (RUSM), evoked by electric field stimulation (EFS), were also significantly reduced by T16Ainh-A01[1]. T16Ainh-A01 (10 μM) inhibits nearly completely TMEM16A chloride current (induced by 275 nM free calcium in the pipette) at all voltages, indicating a voltage-independent block mechanism[2]. T16Ainh-A01 led to the significant repression of cell proliferation, cell migration, and collagen secretion in CFs(cardiac fibroblasts)[3]. Suppression of ANO1 activity either by selective inhibitor (T16Ainh-A01) or by siRNA significantly attenuated the migration and invasion of ATC (Anaplastic thyroid carcinoma) cells[4].
T16Ainh-A01 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse retinal rod bipolar cells
10 µM
200 milliseconds
Inhibited outward rectifying current, confirming the voltage-dependent component of ANO1
Cells. 2020 Feb 26;9(3):543
SH-SY5Y cells
10–30 µM
24 hours
Evaluate the effect of T16Ainh-A01 on HRSV-GFP expression, results showed significant reduction in HRSV-GFP expression
Thorax. 2021 Jan;76(1):64-72
A549 cells
5–30 µM
24 hours
Evaluate the effect of T16Ainh-A01 on HRSV-GFP expression, results showed significant reduction in HRSV-GFP expression
Thorax. 2021 Jan;76(1):64-72
HaCaT keratinocytes
30 µM
3 days
Inhibition of HaCaT cell proliferation and reduction of pERK1/2 phosphorylation
Int J Mol Sci. 2021 Jul 1;22(13):7145
Vascular smooth muscle cells (VSMCs)
10 µM
30 minutes
Inhibiting TMEM16A activity, significantly reducing the expression of VCAM-1 and ICAM-1
Biomedicines. 2022 Oct 31;10(11):2760
Mouse retinal rod bipolar cells
40 µM
300 seconds
Inhibited ANO1 tail current (I tail), indicating ANO1 is activated by Ca2+
Cells. 2020 Feb 26;9(3):543
Mouse cardiac vascular endothelial cells (CVECs)
30 µM
48 hours
To evaluate the effect of T16Ainh-A01 on CVECs proliferation, results showed T16Ainh-A01 did not affect cell growth
Br J Pharmacol. 2014 Aug;171(15):3680-92
Dorsal root ganglia neurons
20 µM and 100 µM
90 seconds
ANO1 blockade with T16Ainh-A01 significantly inhibited the PGE2-evoked axonal depolarisation
Sci Rep. 2024 Jul 29;14(1):17360
T16Ainh-A01 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6N mice
Cerulein-induced acute pancreatitis model
Intraperitoneal injection
1 mg/kg
Single injection, lasting 12 hours
To investigate the effect of T16Ainh-A01 on the acute pancreatitis mouse model, results showed that T16Ainh-A01 ameliorated pancreatic damage and reduced IL-6 levels in serum and pancreatic tissues.
J Adv Res. 2020 Jan 21;23:25-35
Genetically epilepsy-prone rats (GEPR-3s)
Genetically epilepsy-prone rat model
Oral
10 mg/kg
Single dose, tested 30 minutes after administration
To evaluate the effects of T16Ainh-A01 on acoustically evoked seizures in GEPR-3s. Results showed that T16Ainh-A01 pretreatment did not significantly alter the incidence of WRSs and GTCSs, seizure latency, seizure duration, or seizure severity.
Biomedicines. 2022 Feb 15;10(2):449
Sprague-Dawley rats
Chronic constriction injury (CCI) model
Intrathecal injection
10 μg
Once every 6 hours, totally five times
To evaluate the effect of T16Ainh-A01 on CCI-induced neuropathic pain. Results showed that T16Ainh-A01 significantly alleviated thermal hyperalgesia, reduced the excitability of DRG neurons, and decreased TMEM16A expression.
Neural Regen Res. 2019 Jun;14(6):1091-1098
Guinea pig
Tracheal rings
Organ baths
10 μM, 50 μM, 100 μM
30-minute intervals
To investigate the relaxant effect of T16Ainh-A01 on acetylcholine-induced contraction. Results showed that 50 μM and 100 μM T16Ainh-A01 significantly relaxed the acetylcholine-induced contraction.
Anesthesiology. 2015 Sep;123(3):569-81
BALB/c mice
IMQ-induced psoriasis-like skin injury model
Topical application on ears
30 µM and 100 µM
Once daily for 7 consecutive days
Alleviation of psoriasis-like symptoms and reduction of ANO1 and pERK1/2 expression
Int J Mol Sci. 2021 Jul 1;22(13):7145
Mice
Pain-related behavior model
Hind paw injection
300 μM
Single injection, observed for 5 minutes
Investigate the effect of ANO1 antagonist T16Ainh-A01 on capsaicin-induced pain-related behaviors, finding that A01 significantly reduced capsaicin-induced pain behaviors
Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):5213-8
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