TRPC5
TRPC5 is a receptor-activated Ca2+-permeable cation channel within the TRPC family, linking extracellular receptor stimulation to intracellular ion entry[1]. Mechanistically, GPCR signaling can act through Gαi3, which binds the TRPC5 ankyrin-repeat edge and increases PIP2 sensitivity, thereby facilitating channel opening[2]. In disease-relevant models, TRPC5 supports amygdala-dependent innate fear behavior, and kidney studies identify TRPC5-mediated Rac1 activation, synaptopodin destabilization, podocyte cytoskeletal remodeling, and albuminuria[3][4]. Compared with related isoforms, TRPC5 forms homotetramers, whereas the human TRPC1/C5 heteromer contains one TRPC1 and three TRPC5 subunits, producing an asymmetric selectivity filter and lower gate distinct from the TRPC5 homomer[5]. For experimental applications, AC1903 specifically blocked TRPC5 channel activity in proteinuric rat glomeruli and suppressed severe proteinuria and podocyte loss in FSGS models[6]. Structural inhibitor studies further mapped human TRPC5 complexes with clemizole and HC-070, supporting rational use of TRPC5 inhibitors in channel-function and disease-model research[7].
References:
- [1]. Hofmann T, et al. Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7461-6. [Content Brief]
- [2]. Won J, et al. Molecular architecture of the Gαi-bound TRPC5 ion channel. Nat Commun. 2023 May 3;14(1):2550. [Content Brief]
- [3]. Riccio A, et al. Essential role for TRPC5 in amygdala function and fear-related behavior. Cell. 2009 May 15;137(4):761-72. [Content Brief]
- [4]. Schaldecker T, et al. Inhibition of the TRPC5 ion channel protects the kidney filter. J Clin Invest. 2013 Dec;123(12):5298-309. [Content Brief]
- [5]. Kim SH, et al. Molecular architecture of the human TRPC1/C5 heteromeric channel. Nat Commun. 2025 Dec 10;17(1):317. [Content Brief]
- [6]. Zhou Y, et al. A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models. Science. 2017 Dec 8;358(6368):1332-1336. [Content Brief]
- [7]. Song K, et al. Structural basis for human TRPC5 channel inhibition by two distinct inhibitors. Elife. 2021 Mar 8;10:e63429. [Content Brief]
-
TRPC5 Related Products (14)
- 1
-
Rosiglitazone
0 ImagesSynonyms: BRL 49653Rosiglitazone (BRL 49653) is an orally active selective PPARγ agonist (EC50: 60 nM, Kd: 40 nM), with blood-brain barrier permeability. Rosiglitazone is an TRPC5 activator (EC50: 30 μM) and TRPM3 inhibitor. Rosiglitazone can be used in the research of obesity and diabetes, senescence, ovarian cancer.
-
Rosiglitazone hydrochloride
0 ImagesSynonyms: BRL 49653 hydrochlorideRosiglitazone (BRL 49653) hydrochloride is an orally active selective PPARγ agonist (EC50: 60 nM, Kd: 40 nM). Rosiglitazone hydrochloride is a TRPC5 activator (EC50: 30 μM) and TRPM3 inhibitor. Rosiglitazone hydrochloride can be used in the research of obesity and diabetes, senescence, ovarian cancer.
-
JD03-02
0 ImagesCat. No.: HY-184164JD03-02 is an orally active, blood-brain barrier-permeable TRPC1/5 heterodimer inhibitor with an IC50 of 0.2 nM. JD03-02 preferentially binds to a unique ligand-binding pocket at the interface of TRPC1-TRPC5, exerts almost no inhibitory effect on TRPC5 homotetramers, and thus avoids side effects such as obesity and hyperkinesia. JD03-02 induces anxiolytic and antidepressant effects in mouse models. JD03-02 can be used in studies related to depression and anxiety disorders.
-
Rosiglitazone potassium
0 ImagesSynonyms: BRL 49653 potassium
-
TRPC antagonist 1
0 ImagesCat. No.: HY-162090CAS No.: 3027139-12-1TRPC antagonist 1 (compound 15g) is a potent TRP channel (TRPC) antagonist with IC50s of 2.4 μM, 12.2 μM, 7.6 μM, 2.9 μM, and 3.4 μM for TRPC3, TRPC4, TRPC5, TPRC6, and TRPC7, respectively. TRPC antagonist 1 displays noteworthy anti-glioblastoma efficacy in vitro against U87 cell lines.
-
TRPC5-IN-5
0 ImagesCat. No.: HY-172106CAS No.: 738603-63-9TRPC5-IN-5 (Compound ph8) is a TRPC5 inhibitor (IC50: 1.28 μM). TRPC5-IN-5 can be used for research of neurological diseases and renal diseases.
-
TRPC4/5-IN-1
0 ImagesCat. No.: HY-146155CAS No.: 3032263-08-1TRPC4/5-IN-1 is a potent TRP channel 4/5 (TRPC4/5) inhibitor with IC50s of 2.06 μM and 0.54 μM, respectively. TRPC4/5-IN-1 can be used for proteinuric kidney diseases and skin inflammatory diseases research.
-
TRPC5-IN-6
0 ImagesCat. No.: HY-162584CAS No.: 3047956-65-7TRPC5-IN-6 (Compound 12) is an orally effective transient receptor potential (TRPC5) inhibitor with a IC50 value of 81 nM. TRPC5-IN-6 has good biosafety and low liver and kidney toxicity, and is expected to play an important role in the treatment of chronic kidney disease (CKD).
-
TRPC4/5-IN-3
0 ImagesTRPC4/5-IN-3 (Compound 32) is the orally active inhibitor for transient receptor potential canonical channel 4/5 (TRPC4/5) with IC50 of 3.6 nM and 5.5 nM. TRPC4/5-IN-3 inhibits hERG channel with IC50 of 6.5 µM. TRPC4/5-IN-3 exhibits good metabolic stability in human/rat/mouse liver microsomes. TRPC4/5-IN-3 exhibits antidepressant and anxiolytic activity in mouse models, exhibits good pharmacokinetic characteristics in mouse with an oral bioavailability of 87%.
-
TRPC5-IN-4
0 ImagesCat. No.: HY-144429CAS No.: 2762315-39-7TRPC5-IN-4 is potent and safe TRPC inhibitor with IC50 value of 14.07 nM and 65 nM for TRPC5 and TRPC4, respectively. TRPC5-IN-4 shows no damage on the cellular component of liver and kidney. TRPC5-IN-4 can be used for the research of chronic kidney disease (CKD).
-
BD-1063
0 ImagesCat. No.: HY-18101CAS No.: 150208-28-9BD-1063 is a selective σ-1 receptor antagonist with inhibitory activity against TRPC5 and TRPM3. BD-1063 exerts anti-hyperalgesic and anti-allodynic effects by inhibiting sustained calcium influx mediated by TRPC5 and TRPM3, and reverses the effects of Carrageenan (HY-125474). BD-1063 also significantly reduces excessive ethanol self-administration behavior. BD-1063 is widely used in studies on the mechanisms underlying neuropathic pain, inflammatory hyperalgesia, and alcohol abuse and dependence.
- 1
