SAR7334 is a highly potent and specific TRPC6 channel inhibitor (IC₅₀=7.9nM). SAR7334 also inhibits TRPC3- and TRPC7-mediated Ca²⁺ influx into cells[1-2]. SAR7334 can be used in research related to fibrotic diseases such as focal segmental glomerulosclerosis, skeletal muscle dysfunction, as well as pulmonary arterial hypertension and pulmonary edema[3-4].
In vitro, hippocampal neurons isolated from young, middle-aged, and aged mice were treated with SAR7334 (0.1μM or 1μM) for 15 minutes. SAR7334 dose-dependently reduced the resting intracellular calcium ([Ca²⁺]ᵣ) and sodium ([Na⁺]ᵣ) concentrations in neurons, with a more pronounced reduction observed in middle-aged and aged neurons compared to young ones[5]. MPC5 podocytes were pretreated with SAR7334 (1μM) for 30 minutes, followed by stimulation with AngII (1μM) for 24 hours. SAR7334 significantly inhibited the expression of TRPC6, AT1R, and Caspase-3 proteins, increased the expression of the podocyte structural proteins Nephrin and Podocin, and reduced intracellular Ca²⁺ fluorescence intensity and cell apoptosis[6].
In vivo, spontaneously hypertensive rats (SHR) were treated with SAR7334 (oral administration; 10mg/kg) for two days. Compared to the vehicle-treated control group, the SAR7334-treated group showed no significant change in mean arterial pressure (MAP)[7]. In establishing a chemotherapy-induced peripheral neuropathy (CIPN) mouse model via cisplatin intervention, SAR7334 (10mg/kg; i.p.) was administered beginning one day before the second cycle of cisplatin treatment and continued for 7 days. SAR7334 significantly alleviated cisplatin-induced CIPN symptoms, including improving the paw withdrawal threshold in mechanical allodynia tests, shortening the response time to an adhesive stimulus, and preventing the loss of intraepidermal nerve fibers and Merkel cells in the plantar skin. Concurrently, SAR7334 ameliorated anxiety-like behaviors in CIPN mice[8].
References:
[1] Ilatovskaya DV, Palygin O, Levchenko V, et al. The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling. Sci Rep. 2017 Mar 22;7(1):299.
[2] Fang X, Dong S, Wu Y, et al. Ameliorated biomechanical properties of carotid arteries by puerarin in spontaneously hypertensive rats. BMC Complement Med Ther. 2021 Jun 22;21(1):173.
[3] Ducrocq GP, Anselmi L, Stella SL Jr, et al. Inhibition and potentiation of the exercise pressor reflex by pharmacological modulation of TRPC6 in male rats. J Physiol. 2025 Sep;603(18):5027-5052.
[4] Obara K, Takahashi S, Otake M, et al. Pharmacological Characteristics of Extracellular Ca2+ Influx Pathways Responsible for Platelet-Activating Factor-Induced Contractions in Rat Esophagus Smooth Muscle: Involvement of L-Type, Receptor-Operated, and Store-Operated Ca2+ Channels. Biol Pharm Bull. 2025;48(6):932-940.
[5] Uryash A, Flores V, Adams JA, et al. Memory and Learning Deficits Are Associated With Ca2+ Dyshomeostasis in Normal Aging. Front Aging Neurosci. 2020 Jul 16;12:224.
[6] Feng Y, Li M, Wang Y, et al. Activation of TRPC6 by AngⅡ Induces Podocyte Injury and Participates in Proteinuria of Nephrotic Syndrome. Front Pharmacol. 2022 Aug 3;13:915153.
[7] Maier T, Follmann M, Hessler G, et al. Discovery and pharmacological characterization of a novel potent inhibitor of diacylglycerol-sensitive TRPC cation channels. Br J Pharmacol. 2015 Jul;172(14):3650-60.
[8] Jiang YY, Li X, Hu FX, et al. Electroacupuncture alleviates chemotherapy-induced peripheral neuropathy and anxiety by reducing TRPC6/PKC-dependent activation of glutamatergic neurons in the paraventricular thalamic nucleus. Neuroscience. 2026 Jan 9;592:97-110.